Device for cardiac therapy

ABSTRACT

A multi-modal cardiotherapy device ( 100 ) includes an anti-arrhythmic unit ( 118 ) for delivering multiple types of anti-arrhythmic therapy to a heart, a cardiac contractility modulating unit ( 108 ) for delivering cardiac contractility modulating signals to the heart, and for applying anti-arrhythmic cardiac contractility modulating signal therapy to the heart, one or more sensing units ( 112 ) for sensing electrical signals related to electrical activity of the heart to provide an output signal, one or more detecting units ( 116 ) operatively connected to the sensing unit(s) ( 112 ) for detecting in the output signal cardiac events of the heart, a controller unit ( 106 ) operatively connected to the anti-arrhythmic unit ( 118 ), the cardiac contractility modulating unit ( 108 ) and the detecting unit(s) ( 116 ). The controller unit ( 106 ) processes the output of the detecting unit(s) ( 116 ) to detect a cardiac arrhythmia or indications of a possible arrhythmia in the heart and controls the application of anti-arrhythmic therapy, anti-arrhythmic cardiac contractility modulating signal therapy, and cardiac contractility modulating therapy to the heart. The device may be an implantable device or a non-implantable device. The device ( 100 ) may also include a pacing unit ( 102 ). Methods are disclosed for using the device for delivering multi-modal cardiotherapy to the heart.

CROSS REFERENCES TO RELATED APPLICATIONS

This patent application is related to and claims priority from commonlyowned U.S. Provisional Patent applications Ser. No. 60/161,328, filedOct. 25, 1999 entitled “CARDIAC CONTRACTILITY MODULATION DEVICE HAVINGANTI-ARRHYTHMIC CAPABILITIES AND A METHOD OF OPERATING THEREOF”, Ser.No. 60/161,899 filed Oct. 27, 1999 entitled “DEVICE FOR CARDIACTHERAPY”, and Ser. No. 60/161,900 filed Oct. 27, 1999 entitled“ANTI-ARRHYTHMIC DEVICE AND A METHOD OF DELIVERING ANTI-ARRHYTHMICCARDIAC THERAPY”, all three Provisional Patent Applications areincorporated herein by reference in their entirety.

FIELD OF THE INVENTION

The present invention relates generally to the field of cardiotherapydevices and more particularly to cardio-therapeutic devices havingcardiac contractility modulation capabilities and including multi-modalanti-arrhythmic therapy capabilities.

BACKGROUND OF THE INVENTION

Anti-arrhythmic cardiac devices are well known in the art. Such devicesinclude implantable and non-implantable devices which are used fordetecting various types of arrhythmic conditions in a cardiac patientand for applying an appropriate anti-arrhythmic therapy to the heart.

For example, various pacemaker devices may detect various types ofbrady-arrhythmias (also known as bradycardias) and provide artificialpacing therapy to one or more cardiac chambers.

Other types of anti-arrhythmic devices such as cardiac defibrillators,and other anti-tachyarrhythmia devices such asdefibrillator/cardioverter devices are designed to detect variousdifferent types of tachy-arrhythmias (also known as tachycardias) suchas ventricular tachycardia (VT) which is a non-fibrillation type oftachy-arrhythmia and ventricular fibrillation (VF), and to provide oneor more types of appropriate anti-tachycardia therapy to the heart suchas anti-tachycardia pacing (ATP) therapy, cardioverting shock therapyand shock defibrillation therapy. Such devices may use multi-tieredtachy-arrhythmia detection algorithms (also known as classificationalgorithms) for distinguishing between VT, VF and supra-ventriculartachycardia (SVT) arising from atrial fibrillation and for applying theproper type of therapy selected from ATP therapy, low or medium energycardioversion shock therapy, and high energy defibrillating shocktherapy.

U.S. Pat. No. 4,403,614 to Engle et al titled “IMPLANTABLECARDIOVERTER”, incorporated herein by reference, discloses animplantable cardioverter/defibrillator device capable of deliveringcardioversion therapy pulses having an energy level lower than necessaryfor defibrillation as well as defibrillating pulses.

Some modern implantable Cardiotherapy devices are adapted to include acombination of various cardiac therapeutic modes. For example,implantable cardio-therapy devices may use a combination ofanti-bradycardia pacing, ATP pacing, cardioversion and automaticdefibrillating shock therapy. U.S. Pat. No. 4,830,006 to Haluska et al.titled “IMPLANTABLE CARDIAC STIMULATOR FOR DETECTION AND TREATMENT OFVENTRICULAR ARRHYTHMIAS”, incorporate herein by reference, discloses acardiac stimulator device which integrates the functions of bradycardiaand anti-tachycardia pacing therapies and cardioversion anddefibrillation shock therapies.

Recently, a new method of cardiotherapy has been introduced formodifying the cardiac contractility by delivering non-excitatoryelectrical signals to the myocardium at a selected time such that theelectrical signals do not result in exciting propagating myocardialaction potentials due to myocardial refractoriness. While suchnon-excitatory electrical signals do not lead to propagating myocardialaction potentials, they may modulate the myocardial contractility innaturally or artificially paced cardiac beats.

Devices for performing this contractility modulating cardiotherapy areknown as excitable tissue control (ETC) devices, and are also known ascardiac contractility modulation (CCM) devices. It is noted that theterms CCM and ETC are interchangeably used throughout the presentapplication and refer to methods for modulating cardiac contractility bydelivering non-excitatory electrical signals to the heart. Similarly,the terms CCM device and ETC device are interchangeably used throughoutthe present application and refer to devices adapted for modulatingcardiac contractility by delivering non-excitatory electrical signals tothe heart.

ETC devices modulate the activity of excitable tissues by application ofnon-excitatory electrical signals to the heart (or other excitabletissues) through suitable electrodes in contact with the tissue. Forexample, ETC devices may be used, inter alia, to increase or decreasethe contractility of cardiac muscle in vitro, in vivo and in situ., asdisclosed in detail in PCT application, International Publication NumberWO 97/25098 to Ben-Haim et al., titled “ELECTRICAL MUSCLE CONTROLLER”,incorporated herein by reference. Other methods and applications of ETCdevices are disclosed in PCT applications commonly-assigned to theassignee of the present application, International Publication Number WO98/10828, titled “APPARATUS AND METHOD FOR CONTROLLING THE CONTRACTILITYOF MUSCLES” to Ben Haim et al., incorporated herein by reference,International Publication Number WO 98/10829, titled “DRUG-DEVICECOMBINATION FOR CONTROLLING THE CONTRACTILITY OF MUSCLES” to Ben Haim etal., incorporated herein by reference and International PublicationNumber WO 98/10830, titled “FENCING OF CARDIAC MUSCLES” to Ben Haim etal., incorporated herein by reference, International Publications NumberWO 98/10831 to Ben Haim et al., titled “CARDIAC OUTPUT CONTROLLER”,incorporated herein by reference.

Further applications of the ETC including devices combining cardiacpacing and cardiac contractility modulation are disclosed in PCTApplication, International Publication No. WO 98/10832, titled “CARDIACOUTPUT ENHANCED PACEMAKER” to Ben Haim et al., co-assigned to theassignee of the present application. Such ETC devices function byapplying non-excitatory electrical field signals of suitable amplitudeand waveform, appropriately timed with respect to the heart's intrinsicelectrical activity to selected cardiac regions. The contraction of theselected regions may be modulated to increase or decrease the strokevolume of the heart. The timing of the ETC signals must be carefullycontrolled since application of the ETC signal to the myocardium at aninappropriate time may be arrhythmogenic. The ETC signals must thereforebe applied to the selected cardiac region within a defined time intervalduring which the selected cardiac region will not be stimulated by theETC signals.

As disclosed in International Publication No. WO 98/10832, the ETCsignals may be timed relative to a trigger signal which is also used asa pacing trigger, or may be timed relative to locally sensed electrogramsignals.

Co-pending U.S. patent application to Mika et al., Ser. No. 09/276,460,Titled “APPARATUS AND METHOD FOR TIMING THE DELIVERY OF NON-EXCITATORYETC SIGNALS TO A HEART”, filed Mar. 25, 1999, assigned to the commonassignee of the present application, the entire specification of whichis incorporated herein by reference, and the corresponding PCTapplication, International Application No. PCT/IL00/00126, InternationalPublication No. WO 00/57952, disclose a method for timing the deliveryof non-excitatory ETC signals to a heart using, inter alia, an alertwindow period for reducing the probability of delivering an improperlytimed ETC signal to the heart due to spurious detection of noise orectopic beats.

Co-pending U.S. patent application Ser. No. 09/328,068 to Mika et al.,titled “APPARATUS AND METHOD FOR COLLECTING DATA USEFUL FOR DETERMININGTHE PARAMETERS OF AN ALERT WINDOW FOR TIMING DELIVERY OF ETC SIGNALS TOA HEART UNDER VARYING CARDIAC CONDITIONS”, filed Jun. 8, 1999, theentire specification of which is incorporated herein by reference, andthe corresponding PCT application, International Application No.PCT/IL00/00310, disclose devices and methods for collecting patient datawhich is usable for the operation of a device for timing of delivery ofETC signals to the heart using, inter alia, a dynamically varying alertwindow period for event sensing.

Co-pending U.S. patent application Ser. No. 09/338,649 to Mika et al.,titled “APPARATUS AND METHOD FOR SETTING THE PARAMETERS OF AN ALERTWINDOW USED FOR TIMING THE DELIVERY OF ETC SIGNALS TO A HEART UNDERVARYING CARDIAC CONDITIONS”, filed Jun. 23, 1999, the entirespecification of which is incorporated herein by reference, and thecorresponding PCT application, International Application No.PCT/IL00/00321, disclose devices and methods for timing of delivery ofETC signals to the heart using, inter alia, a dynamically varying alertwindow period for event sensing.

Application of ETC therapy to the heart may enhance the cardiac outputwithout increasing the heart rate. Such therapy may be advantageouslyapplied, inter alia, to patients having no diagnosed cardiac rhythmabnormalities as well as to patients such as congestive heart failure(CHF) patients which are particularly prone to episodes of VT or VF.Since cardiac patients such as, inter alia, CHF patients may benefitfrom the use of implantable or non-implantable anti-arrhythmic devices,such as defibrillator, Defibrillator/cardioverter devices and the like,it may be advantageous to implement a single device which is capable ofdelivering anti-arrhythmic therapy and ETC therapy to a cardiac patient.For example, such a device may be capable of delivering ETC therapy anddefibrillating shock therapy to a patient, when a need for such therapyis detected.

While the various methods of timing the delivery of ETC signals to theheart disclosed in the above co-pending U.S. patent application Ser.Nos. 09/276,460, 09/328,068 and 09/338,649 to Mika et al., and in thecorresponding PCT applications, greatly reduce the probability ofinducing arrhythmias due to delivery of ETC signals to the heart at avulnerable time, it may be desirable to include anti-arrhythmiacapabilities in ETC or CCM devices as a safety device in case ofoccurrence of tachy-arrhythmia episodes such as VT or VF, either due toa delivered ETC signal or spontaneously.

Unfortunately, the delivery of ETC signals to the myocardium may lead toelectrical artifact signals sensed by the sense electrodes of theanti-arrhythmic device. Such electrical artifact signals may beerroneously detected by the event detecting circuitry of theanti-arrhythmic device as electrical events representing cardiacactivation. Such spurious detection of electrical artifacts induced byETC signals may adversely affect the detection and/or classification ofcardiac tachy-arrhythmias. For example, such spurious event detectionmay result in classification of a normal heart rate as VT or VF leadingto unnecessary and potentially dangerous defibrillating shock therapybeing delivered to the heart.

Besides the increased patient risk and patient discomfort caused by suchunnecessary delivery of defibrillation shock therapy, such erroneousdetection of VF followed by defibrillating shock therapy may lead tounnecessary drain on the battery of the device, thus shortening theuseful life in implanted devices. Additionally, in devices capable ofdelivering cardioversion therapy, spurious event detection caused by ETCinduced electrical artifacts may result in unnecessary delivery ofcardioversion therapy by the device which has the disadvantage ofunnecessary battery drain and which may increase patient risk.

Another problem which may result from delivering of ETC signals to theheart of a patient which is monitored by an anti-arrhythmic device suchas, inter alia, a defibrillator/cardioverter device, is the possibleinterference of ETC induced electrical artifacts with the operation ofdetection circuitry utilizing automatic gain control (AGC) or automaticthreshold control (ATC). AGC methods and ATC methods are well known inthe art. For example, AGC and ATC methods are disclosed by Dennis A.Brumwell et al., in Chapter 14 titled “THE AMPLIFIER: SENSING THEDEPOLARIZATION” in the book titled “IMPLANTABLE CARDIOVERTERDEFIBRILLATOR THERAPY: THE ENGINEERING-CLINICAL INTERFACE”, pp. 275–302,Eds. Mark W. Kroll and Michael H. Lehmann, Kluwer Academic Publishers,USA, 1997.

ETC signal induced artifacts sensed by the defibrillator amplificationcircuits may cause an undesirable decrease in the gain of the amplifiercircuits in defibrillators using AGC based algorithms which may lead tofailure to detect VF signal. ETC signal induced artifacts sensed by thedefibrillator amplification circuits may also cause an undesirableincrease in the threshold level in defibrillators using ATC basedalgorithms which may also lead to failure to detect VF signal.

The above described interference problems may be encountered in theoperation of a variety of different prior art internal cardiacdefibrillator (ICD) devices and automatic internal cardioverterdefibrillator (AICD) devices, including tiered therapy devices capableof delivering different types of cardiac therapy such asanti-brady-arrhythmic pacing therapy, anti-arrhythmic cardioversiontherapy, anti-arrhythmic defibrillating shock therapy, variable energyshock therapy, anti-tachycardia pacing therapy (ATP) and any combinationthereof. In the presence of ETC signals delivered by operating CCM orETC devices.

SUMMARY OF THE INVENTION

There is therefore provided, in accordance with a preferred embodimentof the present invention, a method for operating a multi-modalcardiotherapy device to deliver multi-modal cardiotherapy to a heart.The method includes the steps of providing a device configured fordelivering cardiac contractility modulating signals, and a plurality ofanti-arrhythmic therapy modalities to the heart, applying cardiaccontractility modulating signals to the heart to modulate thecontractility of at least a portion of the heart, detecting anarrhythmia or indications of possible arrhythmia in the heart deliveringto the heart an anti-arrhythmic therapy selected from the plurality ofanti-arrhythmic therapy modalities based on the type of the arrhythmiaor the indications detected in the step of detecting, and coordinatingthe application of cardiac contractility modulating signals of the stepof applying with the delivering of the anti-arrhythmic therapy of thestep of delivering.

There is also provided, in accordance with a preferred embodiment of thepresent invention, a method for operating a multi-modal cardiotherapydevice to deliver multi-modal cardiotherapy to a heart, the device isconfigured for delivering cardiac contractility modulating signals and aplurality of anti-arrhythmic therapy modalities to the heart. The methodincludes the steps of applying cardiac contractility modulating signalsto the heart to modulate the cardiac output of the heart, detecting anarrhythmia or indications of possible arrhythmia in the heart,delivering to the heart an anti-arrhythmic therapy selected from theplurality of anti-arrhythmic therapy modalities based on the type of thearrhythmia or the indications detected in the step of detecting, andcoordinating the application of cardiac contractility modulating signalsof the step of applying with the delivering of the anti-arrhythmictherapy of the step of delivering.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the plurality of antiarrhythmic therapy modalitiesincludes cardiac contractility modulating signal anti-arrhythmic therapyand one or more anti arrhythmic therapy modalities selected fromdefibrillating shock therapy, cardioverting shock therapy,anti-tachycardia pacing therapy, variable energy shock therapy,anti-bradycardia pacing therapy and any combination thereof.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the cardiac contractility modulating signalanti-arrhythmic therapy includes delivering one or more of the cardiaccontractility modulating signals to the heart for reducing theprevalence of arrhythmic episodes detected in the heart.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the step of applying cardiac contractility modulatingsignals to the heart is performed for modulating the cardiac output ofthe heart.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the step of coordinating includes the step ofterminating the applying of cardiac contractility modulating signals tothe heart of the step of applying, prior to or upon the delivering tothe heart of the anti-arrhythmic therapy.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the step of coordinating includes the step ofrenewing the applying of cardiac contractility modulating signals to theheart after the delivering to the heart of the anti-arrhythmic therapyis terminated.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the indications of possible arrhythmia include thedetection of T-wave alternans in the heart.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the step of detecting further includes the step ofdetermining the heart rate of the heart and disabling the applying ofthe cardiac contractility modulating signals to the heart within theduration of a cardiac contractility modulating signal free time periodif the heart rate is larger than a first threshold value.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the step of detecting further includes the step ofenabling the applying of the cardiac contractility modulating signals tothe heart if no arrhythmia or indications of possible arrhythmia aredetected within the duration of the cardiac contractility modulatingsignal free time period.

There is further provided, in accordance with a preferred embodiment ofthe present invention, a multi-modal cardiotherapy device. The deviceincludes an anti-arrhythmic unit for delivering anti-arrhythmic therapyto the heart. The device also includes a cardiac contractilitymodulating unit configured for delivering cardiac contractilitymodulating signals to the heart for modulating the cardiac contractilityof at least a portion of the heart, and for applying anti-arrhythmiccardiac contractility modulating signal therapy to the heart. The devicealso includes a sensing unit for sensing electrical signals related toelectrical activity of the heart to provide an output signal. The devicealso includes a detecting unit operatively connected to the sensing unitfor receiving the output signal of the sensing unit and for detecting inthe output signal cardiac events of the heart. The device also includesa controller unit operatively connected to the anti-arrhythmic unit, thecardiac contractility modulating unit and the detecting unit, forprocessing the output of the detecting unit to detect a cardiacarrhythmia or indications of possible arrhythmia, for controlling theapplication of the anti-arrhythmic therapy by the anti-arrhythmic unit,and for controlling the application of the anti-arrhythmic cardiaccontractility modulating signal therapy, and the modulating of thecardiac contractility of the portion of the heart by the cardiaccontractility modulating unit. The device also includes at least onepower source for providing power to the anti-arrhythmic therapy unit,the cardiac contractility modulating unit, the sensing unit thedetecting unit, and the controller unit.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the anti-arrhythmic unit is configured for deliveringto the heart multiple modes of anti-arrhythmic therapy selected fromanti-bradycardia pacing therapy, defibrillating shock therapy,cardioverting shock therapy, anti-tachycardia pacing therapy, variableenergy shock therapy, and any combination thereof.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the controller unit is configured for coordinatingthe application to the heart of anti-arrhythmic therapy by theanti-arrhythmic unit with the application to the heart of theantiarrhythmic cardiac contractility modulating signal therapy by thecardiac contractility modulating unit.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the controller unit is configured for coordinatingthe application to the heart of anti-arrhythmic therapy by theanti-arrhythmic unit with the modulating of the cardiac contractility bythe cardiac contractility modulating unit.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the antiarrhythmic unit includes a pacing unitconfigured for pacing at least one chamber of the heart.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the cardiac contractility modulating unit isconfigured for controllably delivering cardiac contractility modulatingsignal anti-arrhythmic therapy to the heart by controllably deliveringone or more of the cardiac contractility modulating signals to the heartfor reducing the prevalence of arrhythmic episodes detected in theheart.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the cardiac contractility modulating unit isconfigured for modulating the cardiac output of the heart by deliveringthe cardiac contractility modulating signals to the heart.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the controller unit is configured for terminating theapplying of cardiac contractility modulating signals to the heart priorto or upon the delivering to the heart of the anti-arrhythmic therapy.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the controller unit is configured for renewing theapplying of cardiac contractility modulating signals to the heart afterthe delivering to the heart of the anti-arrhythmic therapy isterminated.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the detecting unit is configured for detecting T-wavealternans in the heart, as an indication of a possible cardiacarrhythmia.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the device further includes electrodes operativelyconnected to the anti-arrhythmic unit, the cardiac contractilitymodulating unit, and the sensing unit, for delivering theanti-arrhythmic therapy to the heart, for applying the cardiaccontractility modulating signals to the heart, and for sensing theelectrical signals, respectively.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the controller unit is configured for determining theheart rate of the heart and for disabling the modulating of the cardiaccontractility of the portion of the heart by the cardiac contractilitymodulating unit within the duration of a cardiac contractilitymodulating signal free time period if the heart rate is larger than afirst threshold value.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the controller unit is configured for enabling themodulating of the cardiac contractility of the portion of the heart bythe cardiac contractility modulating unit if no arrhythmia orindications of possible arrhythmia are detected within the duration ofthe cardiac contractility modulating signal free time period.

There is also provided, in accordance with a preferred embodiment of thepresent invention, a multi-modal cardiotherapy device. The deviceincludes anti-arrhythmic means for delivering multiple modes ofantiarrhythmic therapy to the heart. The device also includes cardiaccontractility modulating means configured for delivering cardiaccontractility modulating signals to the heart, for modulating thecardiac contractility of at least a portion of the heart, and forapplying anti-arrhythmic cardiac contractility modulating signal therapyto the heart. The device also includes sensing means for sensingelectrical signals related to cardiac activity sensed at the heart. Thedevice also includes detecting means operatively connected to thesensing means for receiving the output signal of the sensing means andfor detecting cardiac depolarization events of the heart. The devicealso includes controller means operatively connected to theantiarrhythmic means, the cardiac contractility modulating means and thedetecting means, for processing the output of the detecting means todetect a cardiac arrhythmia or indications of possible arrhythmia, forcontrolling the application of the anti-arrhythmic therapy modes by theanti-arrhythmic means, and for controlling the application of theanti-arrhythmic cardiac contractility modulating signal therapy, and themodulating of the cardiac contractility by the cardiac contractilitymodulating means. The device also includes means for providing power tothe anti-arrhythmic means, the cardiac contractility modulating means,the sensing means, the detecting means and the controller means.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the anti-arrhythmic means is configured fordelivering to the heart multiple modes of anti-arrhythmic therapyselected from anti-bradycardia pacing therapy, defibrillating shocktherapy, cardioverting shock therapy, anti-tachycardia pacing therapy,variable energy shock therapy, and any combination thereof.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the controller means is configured for coordinatingthe application to the heart of anti-arrhythmic therapy by theanti-arrhythmic means with the application to the heart of theanti-arrhythmic cardiac contractility modulating signal therapy by thecardiac contractility modulating means.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the controller means is configured for coordinatingthe application to the heart of antiarrhythmic therapy by theanti-arrhythmic means with the modulating of the cardiac contractilityby the cardiac contractility modulating means.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the anti-arrhythmic means includes pacing meansconfigured for pacing at least one chamber of the heart.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the cardiac contractility modulating means isconfigured for controllably delivering cardiac contractility modulatingsignal anti-arrhythmic therapy to the heart by controllably deliveringone or more of the cardiac contractility modulating signals to the heartfor reducing the prevalence of arrhythmic episodes detected in theheart.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the cardiac contractility modulating means isconfigured for modulating the cardiac output of the heart by deliveringthe cardiac contractility modulating signals to the heart.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the controller means is configured for terminatingthe applying of cardiac contractility modulating signals to the heartprior to or upon the delivering to the heart of the anti-arrhythmictherapy.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the controller means is configured for renewing theapplying of cardiac contractility modulating signals to the heart afterthe delivering to the heart of the anti-arrhythmic therapy isterminated.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the detecting means is configured for detectingT-wave alternans in the heart, as an indication of a possible cardiacarrhythmia.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the device further includes electrode meansoperatively connected to the anti-arrhythmic means, the cardiaccontractility modulating means and the sensing means, for delivering theanti-arrhythmic therapy to the heart, for applying the cardiaccontractility modulating signals to the heart, and for sensing theelectrical signals, respectively.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the controller means is configured for determiningthe heart rate of the heart and for disabling the modulating of thecardiac contractility of the portion of the heart by the cardiaccontractility modulating means within the duration of a cardiaccontractility modulating signal free time period if the heart rate islarger than a first threshold value.

Finally, in accordance with another preferred embodiment of the presentinvention, the controller means is configured for enabling themodulating of the cardiac contractility of the portion of the heart bythe cardiac contractility modulating means if no arrhythmia orindications of possible arrhythmia are detected within the duration ofthe cardiac contractility modulating signal free time period.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is herein described, by way of example only, withreference to the accompanying drawings, in which like components aredesignated by like reference numerals, wherein:

FIG. 1 is a schematic functional block diagram illustrating a prior artdefibrillator device;

FIG. 2 is a schematic diagram illustrating a cardiac contractilitymodulating device having anti-arrhythmic therapy capabilities, inaccordance with a preferred embodiment of the present invention;

FIG. 3 is a schematic diagram illustrating a detail of a cardiaccontractility modulating device having anti-arrhythmic therapycapabilities, useful in understanding possible implementation methods ofcontrol signals at different levels of a part of the cardiaccontractility modulating device of the present invention;

FIG. 4 is a schematic diagram illustrating a CCM device havingcapability of applying a plurality of different anti-arrhythmic therapymethods to the heart, in accordance with another preferred embodiment ofthe present invention; and

FIGS. 5–8 are schematic diagrams illustrating different implantable andnon-implantable preferred embodiments of the anti-arrhythmic device ofthe present invention which are adapted for delivering CCM signalshaving anti arrhythmic effects to the heart.

DETAILED DESCRIPTION OF THE INVENTION

The following terms are used throughout the application:

Term Definition AC Alternating Current AGC Automatic Gain Control AICDAutomatic Internal Cardioverter Defibrillator ATC Automatic ThresholdControl ATP Anti-Tachycardia Pacing CCM Cardiac Contractility ModulatingCHF Congestive Heart Failure CS Coronary Sinus DC Direct Current ECDExternal Cardiac Defibrillator ECG Electro Cardiogram ETC ExcitableTissue Control GCV Great Cardiac Vein ICD Internal Cardiac DefibrillatorIEGM Intracardiac Electrogram LUT Look Up Table LV Left Ventricle LVPLeft Ventricular Pressure PVC Premature Ventricular contraction RA RightAtrium RV Right Ventricle SVT Supra Ventricular Tachycardia VFVentricular Fibrillation EB's Ectopic Beats VT Ventricular Tachycardia

Reference is now made to FIG. 1 which is a schematic functional blockdiagram illustrating a prior art defibrillator device.

The defibrillator device 1 includes a filter and voltage protection unit3 which is suitably electrically connected to sensing electrodes 4A and4B which are implanted in or about the heart 2. The filter and highvoltage protection unit 3 may includes various types of filteringcircuitry for filtering the electrical signals sensed by the sensingelectrodes 4A and 4B to remove signal components having undesirablefrequencies (such as electrical noise at mains frequencies or otherfilterable noise) and for protecting the other circuitry of thedefibrillator device 1 from high voltage signals resulting from thedelivery of the electrical defibrillating shocks to the heart 2. Thedefibrillator 1 further includes a sensing unit 8 which is electricallyconnected to the filter and high voltage protecting unit 3.

The sensing unit 8 may include amplification circuitry for amplifyingthe filtered electrical signals. The output of the sensing unit 8 issuitably connected to a detecting circuit which performs the detectionof electrical depolarization events representing cardiac activation. Thedetecting unit may be any analog or digital unit which is capable ofdetecting cardiac depolarization events by comparing it to a detectionthreshold as is known in the art or by any other event detection methodwhich is known in the art. For example, the sensing unit 8 and thedetecting unit 10 may be implemented using analog circuitry as disclosedby Dennis A. Brumwell et al. In Chapter 14 titled “THE AMPLIFIER:SENSING THE DEPOLARIZATION” of the book titled “IMPLANTABLE CARDIOVERTERDEFIBRILLATOR THERAPY: THE ENGINEERING-CLINICAL INTERFACE”, pp. 275–302,Eds. Mark W. Kroll and Michael H. Lehmann, Kluwer Academic Publishers,USA, 1997, incorporated herein by reference. However, The sensing unit 8and the detecting unit 10 may also be implemented by other differentanalog or digital circuits or any combinations thereof as is known inthe art of defibrillators.

The defibrillator device 1 further includes a microprocessor unit 12connected to the detecting unit 10 to receive therefrom signalsrepresenting the detection of cardiac depolarization events. Themicroprocessor unit 12 is also connected to Timing unit(s) 14 forreceiving timing signals therefrom, and to memory unit(s) 16. The memoryunits 16 may be one or more memory devices for storing and retrievingdata. The memory unit(s) 16 may include read-only memory devices andread-write memory devices for storage and retrieval of data. The timingunit(s) 14 and the memory unit(s) 16 communicate with the microprocessorunit 12 through a data bus 15.

The microprocessor 12 is also connected to a defibrillating unit 18which is controlled by the microprocessor unit 12. The defibrillatingshock unit 18 is designed to deliver electrical defibrillating shocks tothe heart 2 through suitable defibrillating electrodes 6A and 6Bdisposed in or about the heart 2. The defibrillating shock unit 18 maytypically include a current source such as a battery (not shown), acharging circuit (not shown), and high voltage output switches (notshown) as is known in the art. For example, the defibrillating shockunit 18 may be implemented as disclosed by C. G. Supino in Chapter 8,titled “THE SYSTEM” pp. 163–172 of the book titled “IMPLANTABLECARDIOVERTER DEFIBRILLATOR THERAPY: THE ENGINEERING-CLINICAL INTERFACE”,Eds. Mark W. Kroll and Michael H. Lehmann, Kluwer Academic Publishers,USA, 1997, incorporated herein by reference. However, the defibrillatorunit 18 may be implemented using any design or circuit for deliveringdefibrillation shocks to the heart which is known in the art.

The defibrillator device 1 also includes a power source 13 for providingpower to the various components of the device 1. The power source 13 issuitably operatively connected (connections not shown for the sake ofclarity of illustration) to provide electrical energy the components ofthe defibrillator device 1 as is known in the art. The power source 13may be an electrochemical cell or a battery (primary or rechargeable),or the like but may be any other suitable power source for providingelectrical power which is known in the art. It is noted that while thepower source 13 is shown as included within the defibrillator device 1,the power source 13 may be also disposed externally to the device 1. Forexample, the power source 13 may be a power source such as, but notlimited to, a conditioned or regulated DC or AC power supply,operatively connected to the mains power supply (not shown) as is knownin the art. Such mains powered external defibrillator devices are wellknown in the art.

It is noted that the defibrillator device 1 of FIG. 1 is given herein byway of a non-limiting example of a prior art defibrillator and that manyother types of defibrillators using different hardware implementationsare possible as is known in the art.

The defibrillator device 1 represents an automatic implantabledefibrillator device (AICD). However, other types of defibrillators suchas external cardiac defibrillator (ECD) devices are also known in theart.

In operation, the sensing unit 8 amplifies the filtered electricalsignals sensed by the sensing electrodes 4A and 4B, the detection unit10 receives the amplified filtered signals and detects depolarizationevents, the detection may employ various methods such as thresholdcrossing detection methods as disclosed by Brumwell et al., including,but not limited to, AGC methods and ATC methods. However any othersuitable event detection methods known in the art may also be used forevent detection. The detecting unit 10 provides to the microprocessorunit 12 detection signals representative of the detection of an event inthe sensed amplified signal provided by the sensing unit 8. Themicroprocessor unit 12 processes the detection signals using processingprograms embedded in the microprocessor unit 12 or in the memory unit(s)16 connected thereto. The various processing algorithms are generallyreferred to as classification algorithms or classification programs. Theclassification programs process the temporal data of the time ofoccurrence of the detection signals and classify the sensed cardiacrhythm as belonging to one of a plurality of possible cardiac rhythmcategories. In a non-limiting example, the categories may include arange of heart rates defined as normal cardiac rate for a particularpatient, an elevated heart rate range classified as a ventriculartachycardia (VT), and another elevated heart rate range classified as aventricular fibrillation (VF). The various classification methods andalgorithms are well known in the art are not the subject matter of thepresent invention and will therefore not be disclosed in detailhereinafter. Some exemplary methods of tachy-arrhythmia detectionmethods are disclosed by Stan M. Bach et al. in Chapter 15 titled“TACHYARRHYTHMIA DETECTION”, pp. 303–323, of the book titled“IMPLANTABLE CARDIOVERTER DEFIBRILLATOR THERAPY: THEENGINEERING-CLINICAL INTERFACE”, Eds. Mark W. Kroll and Michael H.Lehmann, Kluwer Academic Publishers, USA, 1997, incorporated herein byreference.

If a VF episode is detected, the microprocessor 12 may based on such adetection output various control signals to the defibrillating shockunit 18 for initiating the charging of a high voltage capacitor (notshown) included in the defibrillating unit 18 in preparation fordelivering a defibrillation shock to the heart. After verification ofdetection of VF further control signals output from the microprocessorunit 12 to the defibrillating unit 18 may initiate the delivering of adefibrillating, shock to the heart 2.

Some prior art defibrillator/cardioverter devices are also capable ofdelivering Anti-tachycardia pacing (ATP) and cardioversion therapy afterdetection of VT, as is well known in the art. For example, such devicesand methods of delivering ATP and cardioversion therapy are disclosed inChapter 16 titled “ANTI-TACHYCARDIA PACING AND CARDIOVERSION” pp.325–342, of the book titled “IMPLANTABLE CARDIOVERTER DEFIBRILLATORTHERAPY: THE ENGINEERING-CLINICAL INTERFACE”, Eds. Mark W. Kroll andMichael H. Lehmann, Kluwer Academic Publishers, USA, 1997, incorporatedherein by reference. Such devices may utilize pacing circuitry (notshown in FIG. 1 for the sake of clarity of illustration) to delivervarious pacing and shock signals to the heart for treating theventricular tachycardia.

It is noted that the term Anti-arrhythmic devices is used throughout thepresent application to indicate devices for delivering anti-arrhythmiatherapy to the heart, the anti-arrhythmia therapy may includedefibrillating shocks suitable for VF termination, anti-arrhythmicpacing therapy suitable for treating tachy-arrhythmias such assupra-ventricular tachycardia (SVT) and other types of ventriculartachycardia (VT), cardioversion therapy, and any combination of theabove therapies with pacing pulses for anti-bradycardia therapy.

Reference is now made to FIG. 2 which is a schematic diagramillustrating a cardiac contractility modulating device havinganti-arrhythmic therapy capabilities, in accordance with a preferredembodiment of the present invention.

The anti-arrhythmic CCM device 30 includes an anti-arrhythmic therapyunit 38 and an a CCM unit 40. The anti-arrhythmic therapy unit 38 isoperatively connected to the CCM unit 40 for receiving control signalstherefrom. The anti-arrhythmic therapy unit 38 is connectable to sensingelectrodes 34A and 34B for sensing cardiac depolarization events asdisclosed hereinabove for prior art defibrillating devices. Theanti-arrhythmic therapy unit 38 is also connectable to a pair of therapydelivering electrodes 32A and 32B, for delivering anti-tachycardiatherapy to the heart 2 through the electrodes 32A and 32B as is known inthe art and disclosed hereinabove. The anti-arrhythmic CCM device 30also includes a power source 165 for providing power to the variouscomponents of the anti-arrhythmic CCM device 30. The power source 165 issuitably operatively connected (connections not shown for the sake ofclarity of illustration) to provide electrical energy the components ofthe anti-arrhythmic CCM device 30, as is known in the art. The powersource 165 may be an electrochemical cell or a battery (primary orrechargeable), or the like but may be any other suitable power sourcefor providing electrical power which is known in the art. It is notedthat while the power source 165 is shown as included within theanti-arrhythmic CCM device 30, the power source 165 may be also disposedexternally to the anti-arrhythmic CCM device 30. For example, the powersource 165 may be a power source such as, but not limited to, aconditioned or regulated DC or AC power supply, operatively connected tothe mains power supply (not shown), as is known in the art.

For example, in accordance with one preferred embodiment of the presentinvention, the anti-arrhythmic therapy unit 38 is a defibrillating shockunit and the electrodes 32A and 32B are defibrillation electrodessuitable for delivering defibrillating shocks to the heart 2, as isknown in the art and disclosed hereinabove.

Alternatively, in accordance with another preferred embodiment of thepresent invention, the anti-arrhythmic therapy unit 38 is an energycardioverting shock unit and the electrodes 32A and 32B arecardiovertion electrodes suitable for delivering cardioverting shocks tothe heart 2, as is known in the art and disclosed hereinabove.

In accordance with yet another preferred embodiment of the presentinvention, the anti-arrhythmic therapy unit 38 is a unit capable ofdelivering anti-tachycardia pacing (ATP) therapy and the electrodes 32Aand 32B are pacing electrodes suitable for delivering ATP therapy pulsesto the heart 2, as is known in the art and disclosed hereinabove.

Furthermore, accordance with yet another preferred embodiment of thepresent invention, the antiarrhythmic therapy unit 38 is a multi-modalanti-arrhythmic therapy unit capable of delivering cardioverting shocktherapy, anti-tachycardia pacing (ATP) therapy, and defibrillating shocktherapy. In such a case, more than one pair of therapy deliveringelectrodes (not shown) may need to be connected to the anti-arrhythmictherapy unit 38. For example, the electrodes 32A and 32B may be pacingelectrodes suitable for delivering ATP therapy pulses to the heart 2, asis known in the art and disclosed hereinabove and additional electrodes(not shown) or electrodes pairs (not shown) may be suitably connected tothe anti-arrhythmic therapy unit 38, such as defibrillating electrodes(not shown) and/or defibrillating/cardioverting electrodes (not shown).

The CCM unit 40 is connectable to a pair of CCM electrodes 36A and 36B(also known as ETC electrodes) and is capable of delivering CCM signals(also known in the art as ETC signals) to the heart through the CCMelectrodes 36A and 36B to modulate cardiac contractility as disclosed byBen Haim et al. and by Mika et al. In the PCT publications andapplications, and in the Co-pending US patent applications referencedhereinabove. It is noted that, the anti-arrhythmic therapy unit 38 maybe any anti-arrhythmia therapy device known in the art and may beimplemented as an analog unit; a digital unit or a hybrid analog anddigital unit.

It will be appreciated by those skilled in the art that theanti-arrhythmic CCM device 30 of FIG. 2 may also be adapted to include apacing unit (not shown). Such a pacing unit may be used in conjunctionwith suitable pacing electrodes (not shown) for pacing the heart 2, forexample, in patients in need of anti-bradycardia pacing. Additionally,the pacing unit (not shown) may be integrated in the anti-arrhythmictherapy unit 38 such that it may be used for delivering ATP therapy ifthe need for such therapy is detected by the anti-arrhythmic therapyunit 38, as is known in the art and disclosed in U.S. Pat. No. 4,830,006to Haluska et al.

It is noted that while the anti-arrhythmic therapy unit 38, isillustrated as being connected to a single pair of sensing electrodes34A and 34B, a single pair of electrodes 32A and 32B for deliveringanti-tachycardia therapy to the heart 2, and a single pair of CCMelectrodes for delivery of CCM signals to the heart 2, many otherelectrode configurations and combinations are possible which are allconsidered to be within the scope of the present invention. For example,the antiarrhythmic therapy unit 38 may be connected to more than one CCMdelivering electrode pair or electrodes (not shown) for delivering CCMsignals to more than one cardiac region. In another example, more thanone pair of sensing electrodes or a plurality of single sensingelectrodes (not shown) may be used for enabling multi chamber sensingand/or pacing, such multi-electrode configurations are disclosed in theabove referenced, PCT publications to Ben Haim et al. and in co-pendingU.S. patent applications Ser. Nos. 09/276,460, 09/328,068 and 09/338,649to Mika et al., and in the corresponding PCT applications.

It is noted that many types of sensing electrodes, pacing electrodes,shock therapy delivering electrodes may be used in conjunction with theanti-arrhythmic CCM device 38 of FIG. 2. Such electrodes are known inthe art and may also be commercially obtained. The electrode types haveto be suitably adapted to the design and implementation of the deviceanti-arrhythmic CCM device 38. For example if the device 38 is adaptedfor use in an intensive care unit it may use epicardial electrodes orother external types of electrodes. In chronically implanted devices,the electrodes may be intracardiac electrodes adapted for sensing,pacing, defibrillation shock delivery electrodes or any other types ofanti-arrhythmia therapy electrodes known in the art.

Preferably, the anti-arrhythmic therapy unit 38 and the CCM unit areboth in communication with a common microprocessor unit (not shown inFIG. 2, For the sake of clarity of illustration). In such a case, themicroprocessor unit (not shown) controls the delivery of CCM signals bythe CCM unit 40 and also sends control signals to the anti-arrhythmictherapy unit 38. The control signals sent from the microprocessor unit(not shown) control the anti-arrhythmic therapy unit 38 to prevent theinterference of the CCM signal induced electrical artifacts frominterfering with the detection of cardiac arrhythmias as is disclosed indetail hereinafter. Alternatively, the anti-arrhythmic therapy unit 38and the CCM unit 40 may each include a dedicated microprocessor unit(the microprocessor units are not shown in FIG. 2, for the sake ofclarity of illustration). In the latter case the microprocessor unit(not shown) of the antiarrhythmic therapy unit 38 is in communicationwith the microprocessor unit (not shown) of the CCM unit 40 to providethe microprocessor unit of the anti-arrhythmic therapy unit 38 with datarepresentative of the time of delivery of CCM signals by the CCM unit40. This data is processed by the microprocessor of the anti-arrhythmictherapy unit 38, or by the microprocessor of the CCM unit 40 or by bothof these microprocessors to prevent the interference of the CCM signalinduced electrical artifacts from interfering with the detection ofcardiac arrhythmias as is disclosed in detail hereinafter.

Briefly, in accordance with a preferred embodiment of the presentinvention the control signals may be used to prevent the sensing of CCMsignal induced artifacts at the sensing level.

In accordance with another preferred embodiment of the present inventionthe control signals may be used to prevent the sensing of CCM signalinduced artifacts at the detecting level.

In accordance with yet another preferred embodiment of the presentinvention the control signals may be used to prevent the sensing of CCMsignal induced artifacts at the sensing and the detecting levelsimultaneously.

Alternatively, in accordance with yet another preferred embodiment ofthe present invention the control signals may be used to prevent theinterference of the CCM signal induced electrical artifacts frominterfering with the detection of cardiac arrhythmias, not by preventingthe sensing or the detecting of the CCM signal induced electricalartifact but by correcting or compensating the error introduced bydetection of the CCM induced artifacts as cardiac events at thearrhythmia classification program level. This correction or compensationis achieved computationally by suitably processing the control signalsindicative of the delivery of an ETC signal.

In operation, the CCM unit 40 may operate to deliver CCM signals to theheart through the CCM electrodes 36A and 36B or through any other pair(not shown) or pairs (not shown) of electrodes applied to more than onecardiac site. The Pair of sensing electrodes 34A and 34B may be commonlyused for feeding the sensed signals to the sensing unit (not shown) ofthe anti-arrhythmic therapy unit 38 and to the sensing unit (not shown)of the CCM unit 40. Alternatively, different separate pairs ofelectrodes (not shown) may be used for sensing by each of theanti-arrhythmic therapy unit 38 and the CCM unit 40. Prior to thedelivery of CCM signals to the heart 2, the CCM unit 40 or themicroprocessor (not shown in FIG. 2) which controls the CCM unit 40delivers control signals to the anti-arrhythmic therapy unit 38. Thesecontrol signal are related to the delivery of the CCM signals and areused by the anti-arrhythmic therapy unit 38 to disable the sensing ofthe CCM related electrical artifacts or to disable the detection ofthese artifacts as cardiac depolarization events.

It is noted that, additional control signals may also be delivered tothe anti-arrhythmic therapy unit 38 during the delivery of a CCM signalto the heart if the method of filtering the artifact signal is employedat the level of a signal filtering unit (not shown) as is disclosed inmore detail hereinafter.

Reference is now made to FIG. 3 which is a schematic diagramillustrating a detail of a cardiac contractility modulating devicehaving anti-arrhythmic therapy capabilities, useful in understandingpossible implementation methods of control signals at different levelsof a part of the cardiac contractility modulating device of the presentinvention.

In FIG. 3, an anti-arrhythmic module 50 is illustrated which isintegrated within a CCM anti-arrhythmic device 51 (only a part of thedevice 51 is shown, for the sake of clarity of illustration). The module50 includes a filtering and voltage protection unit 53, which receivesinput signals from sensing electrodes (not shown) disposed in or aboutthe heart and is connected to a sensing unit 58. The filtering andvoltage protection unit 53 is operative to filter the signals from thesensing electrodes and to protect the sensing unit 58 connected theretofrom the high energy defibrillating shock related signals, as is knownin the art and disclosed hereinabove.

The sensing unit 58 amplifies the signal received from the sensingelectrodes (not shown) The sensing unit 58 is connected to a detectingunit 60 which detects depolarization events in the filtered amplifiedsignals at the output of the sensing unit 58 as disclosed in detailhereinabove for the prior art defibrillator 1 of FIG. 1. The detectingunit 60 is operatively connected to a microprocessor unit 62.

The microprocessor unit 62 is operatively connected to ananti-arrhythmic therapy unit 68 and controls the delivery ofanti-arrhythmic therapy signals to the heart 2 by controlling the outputof anti-arrhythmic therapy signals from anti-arrhythmic therapy unit 68.The anti-arrhythmic therapy unit 68 may be any type of device or unitknown in the art for delivering one or more anti-arrhythmic type oftherapy to the heart. For example, the anti-arrhythmic therapy unit 68may be a defibrillator unit, a cardioverter/defibrillator unit, or amulti-modal cardiac therapy unit similar to the cardiac stimulatordisclosed by Haluska et al. in U.S. Pat. No. 4,830,006, or any othertype of anti-arrhythmic therapy unit known in the art.

The anti-arrhythmic module 50 receives control signals from other parts(not shown in detail) of the CCM device 51 within which it isintegrated. The control signals may be received from the CCM unit (notshown) which is also integrated within the CCM device 51, or from amicroprocessor or controller unit (not shown) which is included in orcommunicating with the CCM unit (not shown). Alternatively, themicroprocessor unit 62 may control the entire CCM device 51, includingthe CCM unit (not shown).

The prevention of interference of the sensed CCM signal inducedelectrical artifacts may be implemented in various ways. In accordancewith one preferred embodiment of the present invention, the preventionof interference is implemented at the sensing level. In thisimplementation, suitable control signals are sent to the sensing unit 58prior to the delivery of each CCM signal to the heart 2. These controlsignals are represented by the dashed arrow 70. Each of the receivedcontrol signals causes the sensing unit 58 to become refractory toincoming input signals from the filtering and voltage protecting unit53. The timing and duration of the control signals are such that thesensing unit 58 becomes refractory to incoming input signals before thedelivery of the CCM signal to the heart and stays refractory for arefractory period having a duration that is sufficient to prevent theCCM induced electrical artifact from being detected as an event by thedetection unit 60. Thus, the refractory period of the sensing unit 58may last longer than the duration of the CCM signal delivered to theheart, to accommodate for the precise shape, amplitude, polarity andduration of the CCM induced artifact as it is sensed by the sensing unit58. The duration of the refractory period may be a fixed duration, ormay be a preset duration that may be programmed, telemetrically ornon-telemetrically, into the memory (not shown) of the CCM device 51based on actual determination of the artifact parameters obtained fromeach individual patient in a recording and measurement session takingplace after implantation of the electrodes in the patient.

Thus, the determination of the duration of the refractory period is donesuch as to take into account the maximal duration of CCM signal inducedelectrical artifact which may be picked up by the sensing electrodes(not shown) and is capable of being erroneously detected as a true eventin the patient in which the device 51 is operative. This maximalduration is preferably determined empirically for each patient by aphysician or cardiologist after collecting data in a test session of thedevice 51 in the patient taking place after electrode implantation. Itis also preferred to add a certain safety margin by increasing therefractory period above the value of the empirically determined maximalduration, this safety margin may be advantageous in preventing erroneousevent detection in cases in which the CCM signal induced electricalartifact has large variability or may show drift over extended periodsof time due to electrode movements or other reasons.

It is noted that some CCM devices may apply to the heart of the samepatient different types of CCM signals having different or varyingsignal parameters, in response to different cardiac conditions or forchanging and controlling the contractility and cardiac output of theheart. The CCM signal parameters that may vary include, but are notlimited to, CCM signal amplitude, CCM signal duration, CCM signalwaveform, and CCM signal polarity.

Thus, if the refractory period duration is a fixed duration, care mustbe taken to select such a duration that is long enough to ensure thatany type of CCM signal which the device 51 is capable of delivering tothe heart will not result in erroneous (spurious) detection of the CCMsignal induced electrical artifact as a detected event. Alternatively,the refractory period may be a variable refractory period and the device51 may be adapted to select a particular value of a refractory periodduration from a preprogrammed look up table (LUT), which includesdifferent refractory period duration values associated with differentCCM signal types. The data in the LUT may be obtained by empirical testsperformed in the patient in a testing or data collection session afterimplantation of the electrodes in each individual patient. Such testsmay record the parameters of the electrical artifacts associated withthe delivery of cardiac contractility modulating signals havingdifferent parameters. The parameters of the recorded electricalartifacts may then be used to determine appropriate refractory periodparameter sets for each different type of deliverable CCM signal toprevent erroneous detection of the electrical artifacts as cardiacevents, as disclosed in detail hereinabove. This method has theadvantage of being individually adapted to each patent, and of enablingthe control of the refractory period on a beat by beat basis.

The sensing unit 58 may receive the control signals from themicroprocessor unit which controls the activation of the CCM unit. Inthe embodiment in which the device 51 includes only one microprocessorunit 62, the sensing unit 58 receives the control signals from themicroprocessor unit 62. If the CCM unit (not shown) of the device 51 iscontrolled by a second microprocessor or controller (not shown) which isnot the microprocessor 62, the control signals for controlling therefractory period of the sensing unit 58 may be received from the secondmicroprocessor or controller.

In accordance with another preferred embodiment of the presentinvention, the prevention of interference is implemented at thedetecting level. In this implementation, suitable control signals aresent to the detecting unit 60 prior to the delivery of each CCM signalto the heart 2. These control signals are represented by the dashedarrow 72. Each received control signal causes the detecting unit 60 tobecome refractory to incoming input signals from the sensing unit 58.The timing and duration of the control signals are such that thedetecting unit 60 becomes refractory to incoming input signals beforethe delivery of the CCM signal to the heart and stays refractory for arefractory period having a duration that is sufficient to prevent theCCM induced electrical artifact from being detected as an event by thedetection unit 60. Thus, the refractory period of the detecting unit 60may last longer than the duration of the CCM signal delivered to theheart, to accommodate for the precise shape, amplitude and duration ofthe CCM induced artifact as it is sensed by the sensing unit 58. Theduration of the refractory period of detecting unit 60 may be a fixedduration, or may be a preset duration that may be programmed,telemetrically or non-telemetrically, into the memory (not shown) of thedevice 51 based on actual determination of the maximal artifactparameters obtained from each individual patient in a recording andmeasurement session taking place after implantation of the electrodes inthe patient.

Similar to the refractory period of the sensing unit 58 disclosedhereinabove, if the refractory period duration of the detecting unit 60is a fixed duration, care must be taken to select such a duration thatis long enough to ensure that any type of CCM signal which the device 51is capable of delivering to the heart will not result in erroneous(spurious) detection of the CCM signal induced electrical artifact as adetected event. Alternatively, the refractory period of the detectingunit 60 may be a variable refractory period and the device 51 may beadapted to select a particular value of a refractory period durationfrom a preprogrammed look up table (LUT) which includes differentrefractory period duration values associated with different CCM signaltypes. The data in the LUT may be obtained by empirical tests performedin the patient in a testing or data collection session afterimplantation of the electrodes in each individual patient. Such testsmay record the parameters of the electrical artifacts associated withthe delivery of cardiac contractility modulating signals havingdifferent parameters. The parameters of the recorded electricalartifacts may then be used to determine appropriate refractory periodparameter sets for each different type of deliverable CCM signal toprevent erroneous detection of the electrical artifacts as cardiacevents, as disclosed in detail hereinabove. This method has theadvantage of being individually adapted to each patient, and of enablingthe control of the refractory period on a beat by beat basis. The methodis adapted for use in CCM devices which are capable of deliveringvariable CCM signals and of adapting one or more of the CCM signalparameters (such as but not limited to the amplitude, duration, waveshape, and polarity of the CCM signal) for controlling the effect of theCCM signals on the cardiac contractility and/or on the cardiac output.In accordance with a preferred embodiment of the present invention,since in such CCM devices, the CCM signals parameters may be varied intime according to, inter alia, detected patent need and patientmetabolic state, the microprocessor unit 62 may select from the LUT theappropriate refractory period parameters which are associated with theparameters of the particular CCM signal which is about to be deliveredto the heart of the patient under the control of the microprocessor unit62. This method has the advantage of being individually adapted to eachpatient and of flexibly and automatically allowing the selection ofrefractory period duration which is adapted to the parameters of thecurrently delivered CCM signal parameters, thus, allowing control of CCMsignal parameters while still efficiently preventing erroneous detectionof the CCM induced electrical artifacts as true events.

The detecting unit 60 may receive the control signals from themicroprocessor unit which controls the activation of the CCM unit. Inthe embodiment in which the device 51 includes only one microprocessorunit 62, the detecting unit 60 receives the control signals from themicroprocessor unit 62. If the CCM unit (not shown) of the device 51 iscontrolled by a second microprocessor or controller (not shown) which isnot the microprocessor 62, the control signals for controlling therefractory period of the detection unit 60 may be received from thesecond microprocessor or controller.

It is noted that, the microprocessor unit 62 may be a microprocessorunit which is dedicated to the module 50 or may be a microprocessor unitwhich is commonly used to control the operation of the entire CCM device51.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the control signals may cause the sensing unit 58 andthe detecting unit 60 to become refractory as disclosed hereinabove.This implementation has the advantage that more power is conserved byputting both the sensing unit 58 and the detecting unit 60 into arefractory state since the power consumption of each of these units issmaller in the refractory period, resulting in increasing the usefullife of the battery (not Shown) or power source (not shown) which powersthe device 51.

It is further noted that the preventing of the sensing and/or thedetecting of CCM induced electrical artifacts as event may also beachieved by controlling the filtering and voltage protection unit 53such as by putting it into a refractory period or by suitablycontrolling the filtering properties thereof such that all the signalsfed into the sensing unit 58 including the CCM related electricalartifact signals are strongly attenuated during a period equivalent tothe duration of the above disclosed refractory period. If the method ofpreventing the sensing and/or the detecting of CCM induced electricalartifacts as true events is achieved by controlling the filteringcharacteristics such as but not limited to the frequency responsecharacteristics of the filtering and voltage protection unit 53, themicroprocessor unit 62 which controls the filtering and voltageprotection unit 53 and/or the CCM unit (not shown) of the device 51 mayalso provide the filtering and voltage protection unit 53 with datarelated to the CCM signal parameters, such as but not limited to CCMsignal amplitude, CCM signal duration, CCM signal waveform, and CCMsignal polarity. This CCM signal parameter related data may be providedby the microprocessor unit 62 to the filtering and voltage protectionunit 53 before and/or during the time of delivery of the CCM signals tothe heart. The CCM signal parameter related data is useful particularlyin cases where one or more of the parameters of the CCM signals isdynamically varied under control of the microprocessor 62, during thedelivery of CCM therapy, because such CCM signal parameter related dataallows the control of the filtering characteristics of the filtering andvoltage protection unit 53 on a beat by beat basis for CCM signalshaving dynamically variable parameters.

It is noted that the filtering and voltage protection unit 53 may beadapted to function as a controlled matched filter which is adapted toreject the CCM signal induced electrical artifact based on a fixed ordynamically varying template or data adapted for maximal rejection ofthe predicted waveform and/or frequency content of the CCM inducedelectrical artifact. Such template or data may be supplied to thefiltering and voltage protection unit 53 by the microprocessor 62 inaccordance with the data of the type and parameters of the CCM signalscheduled to be delivered to the heart in accordance with the CCMdelivery control program operative on the microprocessor unit 62.

In accordance with still another preferred embodiment of the presentinvention, the prevention of interference of the CCM induced electricalartifact signals is implemented at the classification level. In thisimplementation, the sensing unit 58 and the detecting unit 60 are notput into a CCM signal related refractory period. The microprocessor 62may receive control signals represented by the dashed arrow 74 from theCCM unit. These control signals are indicative of the timing of deliveryof the CCM signals to the heart. Alternatively, in cases wherein themicroprocessor 62 also controls the activation of the CCM unit (notshown) of the device 51, the microprocessor 62 has internal datatherewithin indicative of the computed timing of activation of the CCMunit. In both of these alternatives the microprocessor unit 62 uses thedata indicative of the timing of the delivery of CCM signals forcomputationally correcting or compensating for the possible errors incomputing the heart rate which may be induced by spurious detection ofthe CCM signal induced artifact as “true” depolarization events. In anon-limiting example, the classification program may subtract the knownnumber of CCM signals delivered to the heart within a certain number ofcardiac beat cycles from the total number of events detected by thedetesting unit 60 within the same beat cycles, preventing possible heartrate classification errors which may have been introduced by anerroneous number of detected events, had the correction not beenapplied.

It will be appreciated that the correction methods which may be used forcorrecting or compensating for erroneous event detection prior toprocessing the data for classification and arrhythmia detection must beadapted to the specific methods, programs and algorithms which are usedfor processing the event detection data and for the classification ofheart rates for arrhythmia detection and classification.

It is noted that, while the method of triggering or inducing arefractory period in one or more of the sensing unit 58, the filteringand voltage protection unit 53 and the detecting unit 60 may provide anadequate solution to the problem of erroneous CCM induced artifactdetection, care must be taken to ensure that the blanking of one or moreof the sensing unit 58, the filtering and voltage protection unit 53 andthe detecting unit 60 during the imposed refractory period will not byitself produce undesirable errors in the estimation of the heart ratedue to the cessation of detection of any electrical events within theimposed refractory period duration. Typically, the CCM signal durationmay vary between approximately 20–50 milliseconds (although lower orhigher duration values may also be used). Some VT episodes in humancardiac patients may exhibit R—R intervals of approximately 250–300millisecond duration. Therefore, when the above disclosed refractoryperiod method is used, the blanking or refractory period may occupyapproximately 20% of the total beat cycle. Thus, it is a definitepossibility that a true event may occur within the refractory period andwill therefore not be detected, which may cause errors in thedetermination of the heart rate. Such errors may eventual lead to wrongclassification of the heart rate by the classification methods orclassification algorithms used and may also undesirably delay or inextreme cases even prevent the delivery of the proper anti-arrhythmictherapy by the anti-arrhythmic module 50 of the device 51. For example,under such circumstances, an episode of VT may be missed ofmisclassified as allowable tachycardia, and VF may be misclassified asVT leading to delay in delivery of the proper type of anti-arrhythmictherapy or to failure to deliver any tachy-arrhythmic therapy.

In order to prevent or at least to reduce the probability of themisclassification and the resulting delay or failure of the properapplication of anti-arrhythmic therapy, the device 51 may be adapted touse a threshold based method to disable the delivery of CCM signals tothe heart when the detected heart rate exceeds a certain threshold.Thus, in accordance with another preferred embodiment of the presentinvention, the device 51 continuously determines the heart rate andclassifies the heart rate, in accordance with any sensing, detecting,and anti-arrhythmic heart rate classification methods or algorithmsknown in the art. Simultaneously, the CCM unit or circuitry operates todetect the need for CCM therapy and to control the delivery of CCMsignals to the heart, in accordance with any of the methods of CCMsignal delivery known in the art or disclosed in any of the abovereferenced published or co-pending patent applications disclosedhereinabove. If the heart rate exceeds a certain threshold level, thisis classified as a suspected tachy-arrhythmia and the microprocessor 62disables the delivery of CCM signals to the heart within a time periodwhich is referred to as the “CCM signal free” period, hereinafter. Thedevice 51 then continues to determine the heart rate within this CCMsignal free period, in the absence of CCM signal delivery. The device 51analyzes and classifies the heart rate in accordance with theclassification criteria based on the detection data obtained by thedevice 51 during the CCM signal free period. The device 51 thendetermines whether any type of anti-arrhythmia therapy is to bedelivered to the heart based on the classification of the heart rateobtained in the CCM free period.

If the classification of the heart rate obtained in the CCM free periodindicates the need to deliver any type of anti-arrhythmic therapy, thedevice 51 continues the disabling of CCM signal delivery and initiatesthe delivery of the required anti-arrhythmic therapy, and continues todeliver any indicated anti-arrhythmic therapy and to determine the heartrate as is known in the art until the anti-arrhythmic therapy isterminated. If the anti-arrhythmic therapy is terminated by the device51, the device 51 enables the delivery of CCM signals to the heart.

If the classification of the heart rate obtained in the CCM free perioddoes not indicate a need to deliver any type of anti-arrhythmic therapy,the device 51 enables the delivery of CCM signals.

Thus, in the above disclosed method of operation of the device 51, theant-arrhythmic detection and classification program, sub-routine oralgorithm takes priority over the CCM delivery control program,sub-routine or algorithm, enabling it to override, interrupt or disablethe CCM signal delivery even under conditions in which the delivery ofCCM signals is called for by the CCM delivery control program to modifycardiac contractility and or cardiac output.

Reference is now made to FIG. 4 which is a schematic diagramillustrating a CCM device having capability of applying a plurality ofdifferent anti-arrhythmic therapy methods to the heart.

The CCM device 100 of FIG. 4 includes a pacing unit 102 connectable toone or more pacing electrodes 104. The pacing unit is suitably connectedto a microprocessor or controller 106. The microprocessor 106 controlsthe pacing unit to deliver pacing pulses to the heart (nor shown) forperforming anti-bradycardia pacing if necessary, as is well known in theart. The CCM device 100 also includes a CCM unit 108 capable ofdelivering CCM signals (also known in the art as ETC signals). The CCMunit 108 is connectable to one or more CCM electrodes 110 for deliveringCCM signals to the heart. The CCM device 100 also includes sensing units112 connectable to one or more sensing electrodes 114 for sensingelectrical signals at or about the heart. The CCM device 100 alsoincludes one or more detecting units 116 which are connected to thesensing unit(s) 112 for receiving amplified sensed signals therefrom andto the microprocessor 106 for providing control signals theretoindicative of detecting depolarization events in the heart. The CCMdevice 100 also includes an anti-tachyarrhythmic unit 118 which isconnected to the microprocessor 106 for receiving control signalstherefrom. The anti-tachyarrhythmic unit 118 is connectable to one ormore anti-arrhythmic therapy electrodes 120 for deliveringanti-arrhythmic therapy to the heart.

The microprocessor unit 106 controls the output of antiarrhythmictherapy signals from the anti-tachyarrhythmic unit 118. Theanti-tachyarrhythmic unit 118 may be any type of device or unit known inthe art for delivering one or more anti-arrhythmic type of therapy tothe heart. For example, the anti-arrhythmic therapy unit 68 may be adefibrillator unit, a cardioverter/defibrillator unit or a multi-modalcardiac therapy unit similar to the cardiac stimulator disclosed byHaluska et al. in U.S. Pat. No. 4,830,006, or any other type ofanti-arrhythmic therapy unit known in the art.

The anti-arrhythmic electrodes 120 are adapted to be suitable for thedelivery of the specific types of antiarrhythmic therapy signals whichthe anti-tachyarrhythmic unit 118 is capable of applying to the heart.For example, the anti-arrhythmic electrodes 120 may comprise one or moreelectrodes adapted for delivering signals to the heart such as, but notlimited to, high energy defibrillating shock signals, non-defibrillatingcardioversion signals, ATP signals, and the like. The microprocessorunit 106 is suitably connected to a data bus 122. The data bus 122 isconnected to one or more memory units 124, one or more timing units 126and to a telemetry unit 128. The microprocessor unit 106 may store andretrieve data on the memory units 124. The memory units 124 may includememory units including embedded read only data such as programs foroperating the microprocessor unit 106 to control and operate the device100. The memory units 124 may also include memory units having read andwrite capabilities for data storage and retrieval (such as, but notlimited to, RAM memory units) for storing, inter alia, patient data,computational results, and programming instructions which aretelemetrically or non-telemetrically communicated to the CCM device 100.The timing units 128 provide timing or clocking signals to themicroprocessor unit 106 over the data bus 122. The microprocessor unit106 communicates with the memory units 124, the timing unit(s) 126 andthe telemetry device 128 over the data bus 122. The telemetry device 128is optional and enables wireless data transmission to and from atelemetry transceiver unit (not shown) disposed outside the patient (notshown).

In operation, the delivery of CCM signals to the heart by the CCM unit108 is controlled based on the output of the detecting units 112 to themicroprocessor unit 106, as disclosed in detail in the above referencedco-pending U.S. patent application Ser. Nos. 09/276,460, 09/328,068 and09/338,649 to Mika et al., and in the corresponding PCT applications.

In accordance with one preferred embodiment of the present invention,the CCM unit 108 provides control signals to one or more of the sensingunits 112 and/or to one or more of the detecting units 116 for inducingrefractory periods in the sensing unit(s) 112 or in the detecting units116 or in the sensing unit(s) 112 and the detecting units 116 asdisclosed in detail hereinabove, for preventing interference of CCMinduced electrical artifact signals with the sensing or the detecting orboth sensing and detecting of depolarization events as disclosedhereinabove. The control signals may be (optionally) provided from theCCM unit 108 to the sensing unit 112 as represented by the dashed arrow130. The control signals may also be (optionally) provided from the CCMunit 108 to the detecting unit(s) 116 as represented by the dashed arrow132. The control signals may also be simultaneously provided to thesensing unit(s) 112 and to the detecting unit(s) 116 as disclosedhereinabove.

Alternatively, in accordance with another preferred embodiment of thepresent invention, the control signals may be provided from themicroprocessor unit 106 to the sensing unit(s) 112 or to the detectingunit(s) 116 or to both of the sensing unit(s) 112 and the detectingunit(s) 116 as disclosed in detail hereinabove. The sensing unit(s) 112or the detecting unit(s) 116 or both the sensing unit(s) 112 and thedetecting unit(s) 116 may be switched by the control signals into arefractory state as disclosed hereinabove.

Furthermore, in accordance with yet another preferred embodiment of thepresent invention, the microprocessor unit 106 may use the data of thetiming of the delivery of CCM signals to the heart for performing acorrecting or compensating method or computation in order to preventerrors at the classification level as disclosed in detail hereinabove.

It is noted that, the sensing units 112 may include a plurality ofsensing units operative for providing sensing at different sites of theheart, such as but not limited to, the right atrium, the rightventricle, the left ventricle of the heart and other different cardiacsites in order to provide the various sensing configurations requiredfor the operation of any of the specific type or configuration of theanti-tachyarrhythmic unit 118 which is implemented in the device 100,any of the specific configurations or modes of anti-bradycardia pacingtherapy which may be implemented on the pacing unit 102, and any of thespecific sensing configurations required for operating the CCM unit 108,including but not limited to, the sensing methods and configurationsdisclosed in the PCT publications to Ben Haim et al. and in theco-pending U.S. patent application Ser. Nos. 09/276,460, 09/328,068 and09/338,649 to Mika et al. referenced hereinabove, and in thecorresponding PCT applications.

In order to prevent or at least to reduce the probability of themisclassification and the resulting delay or failure of the properapplication of antiarrhythmic therapy, the device 100 is adapted to usethe threshold based method to disable the delivery of CCM signals to theheart when the detected heart rate exceeds a certain threshold as isdisclosed in detail for the device 51 of FIG. 3.

Thus, in accordance with a preferred embodiment of the presentinvention, the device 100 continuously determines the heart rate andclassifies the heart rate, in accordance with any sensing, detecting,and anti-arrhythmic heart rate classification methods or algorithmsknown in the art. Simultaneously, the CCM unit 108 and themicroprocessor unit 106 operate to detect the need for CCM therapy andto control the delivery of CCM signals to the heart in accordance withany of the methods of CCM signal delivery known in the art or disclosedin any of the above referenced published or co-pending patentapplications disclosed hereinabove. If the heart rate exceeds a certainthreshold level, this heart rate is classified as a suspectedtachy-arrhythmia and the microprocessor 106 disables the delivery of CCMsignals to the heart within the CCM signal free period, disclosedhereinabove.

Typically, the heart rate is determined by determining the R—R intervalas is known in the art, but other methods may also be used.

The threshold level value for determining the suspected tachy-arrhythmiais preferably individually adapted to each patient and then set byprogramming it into the memory unit(s) 124 by communicating ittelemetrically or non-telemetrically to the device 100 as is known inthe art. This individual determination and setting of the value of theheart rate threshold level for suspected tachy-arrhythmia has theadvantage of enabling to fine-tune the operation of the device 100 suchas to find an appropriate balance between minimizing undesired masking,delayed detection, or non-detection of therapy requiringtachy-arrhythmic episodes due to use of the above disclosed refractoryperiod and maximizing the upper heart rate level at which CCM therapymay still be delivered to the heart.

The precise value of the acceptable threshold level may be influenced,inter alia, by the type of cardiac disorder of the patient, the presenceor absence of cardio-therapeutic drugs used by the patient, and datacollected in the same patient under normal cardiac conditions, SVTconditions, VT conditions and possibly VF conditions. The setting of thethreshold value may have to be performed by a physician orcardio-physiologist based on study of such patient conditions and on thedegree of desired CCM modification for that patient.

Typically, an exemplary non-limiting value for the heart rate thresholdlevel is 150 heart beats per minute. However, other larger or smallerthreshold level values may also be used, according to the individualpatient cardiac conditions.

The disabling of the delivery of CCM signals is performed by themicroprocessor unit 106 by sending appropriate control signal or signalsto the CCM unit 108. The device 100 then continues to determine theheart rate within this CCM signal free period in the absence of CCMsignal delivery. The microprocessor 106 of the device 100 analyzes andclassifies the heart rate in accordance with the classification criteriabased on the detection signal data which are sent from one or more ofthe detecting units 116 to the microprocessor unit 106 during the CCMsignal free period. The microprocessor 106 of the device 100 thendetermines whether any type of anti-arrhythmia therapy is to bedelivered to the heart based on the classification of the heart rateobtained in the CCM free period.

If the classification of the heart rate resulting from the processing ofthe detection data obtained in the CCM free period indicates the need todeliver any type of anti-arrhythmic therapy, the microprocessor 106continues the disabling of CCM signal delivery and initiates thedelivery of the required antiarrhythmic therapy by sending appropriatecontrol signals to the anti-tachyarrhythmic unit 118, and continues todeliver any indicated antiarrhythmic therapy and to determine andclassify the heart rate as is known in the art until the anti-arrhythmictherapy is terminated. If the anti-arrhythmic therapy is terminated bythe microprocessor 106, the microprocessor 106 enables the delivery ofCCM signals to the heart by sending a suitable enabling control signalto the CCM unit 108.

If the classification of the heart rate obtained in the CCM free perioddoes not indicates a need to deliver any type of anti-tachyarrhythmictherapy, the microprocessor 106 enables the delivery of CCM signals tothe heart by sending a suitable enabling control signal to the CCM unit108.

Similar to the method disclosed for the device 51 of FIG. 3, theanti-tachyarrhythmia detection and classification program, sub-routineor algorithm operative on the microprocessor unit 106 takes priorityover the CCM delivery control program, subroutine or algorithm which isalso operative on the microprocessor unit 106, enabling it to override,interrupt, or disable the CCM signal delivery even under conditions inwhich the delivery of CCM signals is called for by the CCM deliverycontrol program to modify cardiac contractility and or cardiac output.

Preferably, but not necessarily, the detection of bradycardia and thedelivery of anti-bradycardia pacing therapy is performed by pacingprograms, subroutines or algorithms which are operative on themicroprocessor 106 as is known in the art and disclosed hereinabove.

It is noted that, if the sensing unit(s) 112 include a plurality ofsensing units operative for providing sensing of signals at differentsites of the heart, the sensing units 112 may be, but need notnecessarily be, identical units and may differ from each other to beadapted for sensing specific signals.

Similarly if the detecting units 116 include a plurality of detectingunits operative for providing event detecting for signals sensed atdifferent sites of the heart, the detecting units 116 may be, but neednot necessarily be, identical units and may differ from each other to beadapted for detection of specific sensed and amplified signals.

it is noted that the CCM devices 30, 51 and 100 of FIGS. 2,3 and 4respectively, may be adapted for acute implantation in a patient forshort term patient monitoring and therapy treatment such as fortemporary use in intensive care hospitalized patient's. Alternatively,the CCM devices 30, 51 and 100 of FIGS. 2,3 and 4 respectively, may beadapted for used as implantable devices for chronic implantation.

Novel Anti-Arrhythmic Effect of CCM Signals

The use of CCM therapy is mainly directed to modulating thecontractility of the heart as is known in the art and disclosedhereinabove. For example, CCM signals may be used for modulatingmyocardial contractility to controllably modulate the cardiac output.Thus, CCM therapy may be used, inter alia, to increase cardiac output inCHF patients or other types of cardiac patients without increasing theheart rate.

While evaluating the results of clinical tests of CCM therapy in humanpatients, originally designed for evaluating the efficacy and safety ofthe CCM therapy (which is also known in the art as ETC therapy), theinventors of the present invention have noticed an unexpectedanti-arrhythmic effect of CCM therapy in the patients.

Experiments Demonstrating a Novel Anti-Arrhythmic Effects of CCM Therapy

The data was gathered in 21 human patients with diagnosed CHF, prior to,during and following the application of CCM therapy.

The CCM therapy was transvenously applied to the patients. In each ofthe patients included in the study, a CARDIMA™ REVELATION™microcatheter, product No. 01-082007, commercially available fromCARDIMA Inc., CA, U.S.A., was introduced through the coronary sinus (CS)into the great cardiac vein (GCV) and positioned in a branch of the GCV.In part of the patients, the microcatheter was positioned in theposterior branch of the GCV. In other patients, the microcatheter waspositioned in the lateral branch of the GCV, and in other patients themicrocatheter was positioned in the anterior branch of the GCV. Thismicrocatheter includes eight coil electrodes which are equally spacedalong the microcatheter and one distal tip electrode that was not usedin the study. The microcatheter was used for the delivery of the CCMsignals through a selected pair of electrodes located on themicrocatheter. Typically, the CCM signals where delivered to the heartthrough a pair of electrodes selected from the six electrodes closest tothe tip of the microcatheter. The CCM signals (also referred to as ETCsignals herein) were delivered using the method based on ventriculartriggering as disclosed in co-pending U.S. patent application Ser. No.09/276,460 to Mika et al., and in the corresponding PCT applications.

The CCM signal used in all of the patients was a square wave with adelay of 20–90 milliseconds from the triggering event, a pulse durationof 20–40 milliseconds, and a current amplitude of 6–15 milliamperes.Each patient was given CCM therapy for a session lasting about an hour,the therapy session consisted of several periods of CCM signal deliveryeach lasting approximately 2–20 minutes. These periods of CCM signaldelivery were separated from each other by intermission time periods ofabout 3–10 minutes. During the intermission time periods no CCM signalswere delivered to the heart of the patients.

The CCM device used for delivering the CCM signals was also capable ofpacing. Each of the patients also had two inserted electrophysiology(EP) diagnostic catheters, one diagnostic catheter was placed in thepatient's right atrium and the other diagnostic catheter was placed inthe patient's right ventricle. The catheters were commercialelectrophysiology catheters such as, the EP diagnostic catheter,catalogue No. F6-QS-010-PS, commercially available from Cordis WebsterIncorporated CA, USA,. All the patients were paced throughout the CCMtherapy session, except for one patient in which the pacing was stoppedfor a portion of the CCM therapy session. When the F6-QS-010-PS EPdiagnostic catheter was used for pacing, the tip electrode and the first(most distal) ring electrode were used for bipolar pacing.

The EP diagnostic catheters were used for sensing and for pacing, as isknown in the art. All the patients were paced using a DDD pacing mode.Some of the patients were paced using a DDD bi-ventricular mode. Inthese patients, bi-ventricular pacing was carried out using the CARDIMA™microcatheter to pace the left ventricle. When the CARDIMA™microcatheter was used for left ventricular pacing the pacing wasbipolar pacing and was applied to the heart transvenously through thesame coil electrode pair that was selected for delivering the CCMsignals to the patient.

The following data were digitized, recorded, and stored as digital dataon the hard disk of a computer for each of the CCM therapy session ofeach patient: the sensed intracardiac electrogram signals (IEGM) in leftventricle (LV), the electrocardiogram signal (ECG lead II), the pacingpulses in each of the relevant pacing electrodes, and the leftventricular pressure (LVP) as determined by a MILLAR® Mikro-Tip®catheter transducer Model SPC-370, commercially available from MILLARINSTRUMENTS Inc, TX, USA.

The pressure catheter was inserted into the LV of each patient usingstandard femoral artery insertion procedures. Another pressure catheterwas used to record the aortic pressure. The data recorded from eachpatient was stored in one or more data files.

When the results of the experiments where evaluated, ectopic beats(EB's) were defined based on the duration of the median R—R interval.For each recorded data file, the R—R intervals were determined. Themedian value of the R—R interval was found for each data file by takingthe median of all the computed R—R intervals for all the beat cycleswithin that data file. All the heart beats of the data file where thenclassified as ectopic beats or normal beats. Any R—R interval thatdeviated by more than ±10% from the median R—R interval of that datafile was classified as an ectopic beat. The remaining R—R intervals inthe data file were classified as normal beats.

For data analysis, all the classified beats from all the sessions of allthe patients were pooled and divided into two groups, a “test” groupincluding all the beats which occurred in the “test periods” and a“control” group including all the beats which occurred in the “controlperiods”. The test periods were defined as a sequence of heart beats inwhich CCM signals were delivered, starting with the third consecutiveheart beat in which a CCM signal was delivered and ending with the lastheart beat in which a CCM signal was delivered (the last heart beat isincluded within the test period). The control period included all theother heart beats in the experiments which were not included in the testperiods. A third group, referred to as the “before CCM” periods group,included all the heart beats occurring during the intermission timeperiods between the periods of CCM signal delivery applications, withthe additional condition that they occurred within the last 60 secondsor less of the intermission time period immediately preceding thebeginning of the next CCM signal delivery period. This is deemed to bethe time within the intermission time period that is least subject tothe effects, if any, of the previous activation of CCM signals in theexperiments.

The results of the analysis are given in TABLE 1 and TABLE 2.

In TABLE 1 and TABLE 2, the first column indicates the condition group,the second column indicates the total number of beats in the group, thethird column indicates the total number of ectopic beats in the group,the fourth column indicates the number of ectopic beats per 1000 beats,and the fifth column indicates the computed 95% confidence level (95%Cl).

The sums indicated in the fourth row (labeled by the word “sum”) of thesecond column of each of TABLE 1 and TABLE 2, represent the sum of thetotal number of beats of the first and second rows of the respectivetable. As defined hereinabove, the “before CCM” periods are part of the“control period”, and are therefore not included in the “sum” of thefourth row to avoid double counting.

TABLE 1 Rate Total (EB's/ Beat Total 1000 95% ALL patients No. EB'sbeats) CI Rate of ectopic beats during “Control 60,239 2,851 47.32 ±1.70period” ; Rate of ectopic beats during “test 53,611 2,170 40.48 ±1.67periods” Rate of ectopic beats during “before 19,019 902 47.42 ±3.02CCM” periods: Sum 113,850

The results of TABLE 1 show that there was a significant reduction of16.9% (Calculated as % reduction=(47.32−40.48)/40.48×100) in the rate ofectopic beats during the delivery of CCM signals to the heart (referredto as the “test period” in TABLES 1 and 2).

The results of the data from all the patients which were notbi-ventricularly paced were pooled and analyzed separately as disclosedhereinabove. The results which are shown in TABLE 2, show a similarreduction in EB rate compared to control.

TABLE 2 Rate (EB's/ Total Total 1000 95% Non-Biventricular patientsbeats EB's beats) CI Rate of ectopic beats during “Control 46,755 2,30249.24 ±1.96 period” Rate of ectopic beats during “test 42,535 1,73540.79 ±1.88 periods” ; Rate of ectopic beats during “before 15,206 71847.22 ±3.37 CCM” periods: Sum 89,290The results of TABLE 2 indicate that there is a significant (p<0.001)reduction in ectopic beats count. (Cl 95%:9.44–19.50) in periods of CCMsignal delivery (the test periods).

The inventors of the present invention have therefore noted that, theseunexpected experimental results indicate that besides the known use ofCCM signals for cardiac contractility modulation and cardiac outputmodulation, the application of CCM signals to the heart may also be usedas a therapeutic treatment for tachyarrhythmic conditions.

Prior art anti-tachyarrhythmia devices, may use the following method todetect and treat tachyarrhythmias, depolarization events are sensed anddetected, the cardiac rhythm is then classified as belonging to a“group” such as for example, slow VT, fast VT, VF the device thendetermines what is the appropriate therapy type based on the results ofthe rhythm classification and on past therapy results. For example, ifATP was attempted and failed for treating fast VT, cardioversion may beattempted. After the arrhythmia type is determined based on theclassification, the selected therapy type is applied to the heart.

Different ICD devices are distinguished, inter alia, by theclassification methods which they use for arrhythmia classification.Most devices use criteria, which are known in the art as “stability” and“onset”, to distinguish different kinds of arrhythmia once a basic ratecomputation led to the detection of arrhythmia. Typically, arrhythmiadetection methods are based on counting depolarization events. However,different devices may use different arrhythmia detection methods. Duringarrhythmia, depolarization events tend to be smaller in amplitude andtherefor harder to detect. This is taken into account by different ratecalculating algorithms differently. Generally, the intervals betweendetected depolarization events are examined. One may look at intervalsbetween events falling within a certain time period, and take a certainpercentage of the shortest ones to determine whether they are shorterthan a certain threshold value. This is known in the art as the “X outof Y criterion”. Alternatively, the device may compute the average ofthe intervals within a time period or of a subgroup of the intervals.Some examples of tachy-arrhythmia detection methods are disclosed byStan M. Bach et al. in Chapter 15 titled “TACHYARRHYTHMIA DETECTION”,pp. 303–323, of the book titled “IMPLANTABLE CARDIOVERTER DEFIBRILLATORTHERAPY: THE ENGINEERING-CLINICAL INTERFACE”, Eds. Mark W. Kroll andMichael H. Lehmann, Kluwer Academic Publishers, USA, 1997, incorporatedherein by reference. However, other arrhythmia detection methods arealso known in the art, including but not limited to methods usingmorphological signal analysis. It is noted that many other methods fordetecting tachy-arrhythmias are known in the art, and that all suchsuitable currently known tachy-arrhythmia detection methods are intendedto be included within the scope of the present invention.

Stability of the heart rate and the speed of onset of the arrhythmia areindicators which are often used to distinguish different types ofarrhythmia as is well known in the art.

It is desirable to detect the onset of arrhythmia as early as possible,in order to have enough time to apply the types of anti-tachyarrhythmictherapy that are less painful to the patient, less energy consuming, andless hazardous, such as ATP, while they might still have effect. Forexample, ATP has very little or no effect in treating VF, but may havegood results in treating slow VT. Usually, heart rate is used toclassify the arrhythmia in order to decide which therapy type to tryfirst. Speed of therapy application is important in order for thetherapy to be effective before the heart deteriorates from slowarrhythmia to faster arrhythmia, and to prevent the heart from becomingmore ischemic, until asystole or clinical death results if no treatmentis timely applied. Stability and onset criteria are used to distinguishVT from SVT to decide whether treatment is necessary, and if so, whichtreatment type to apply. Therefore, many anti-tachyarrhythmic devicesmonitor the rate and onset of an arrhythmia.

It is noted that a tachyarrhythmia is classified as a sequence ofectopic beats by the classification method that was used in the analysisof the experimental data presented in TABLE 1 and TABLE 2. Thus, the“ectopic beat” (EB's) class in the experiments included doublet andtriplet ectopic events. It is also noted that generally,tachy-arrhythmias start as a sequence of ectopic beats which evolvesinto an arrhythmic sequence.

Thus, in accordance with a preferred embodiment of the presentinvention, an anti-arrhythmia device is disclosed which is adapted toinclude the delivery of CCM signals to the heart in response to thedetection of a cardiac tachy-arrhythmia. Such a device may utilize theabove disclosed unexpected effect of CCM signal delivery to reduce therate of occurrence of ectopic beats as a therapeutic means to stop ordiminish the detected tachyarrhythmia.

Furthermore, the present invention discloses a new method for operatingan anti-arrhythmic device having CCM signal delivery capabilities. Themethod comprises the controlled application of CCM signal delivery inresponse to the detection of a tachyarrhythmia by the device.

The delivery of CCM signals as means for achieving anti-arrhythmiatherapy may be performed using CCM delivery timing methods and devicesas disclosed in detail in the above referenced co-pending U.S. patentapplications Ser. Nos. 09/276,460, 09/328,068 and 09/338,649 to Mika etal., and in the corresponding PCT applications. The CCM signalparameters may be the square current pulse parameters disclosedhereinabove in the clinical experiments performed in the CHF patients,but may also be any other suitable CCM signal parameters which areeffective for treating tachyarrhythmias. Various different forms of CCMsignals are known in the art and disclosed in the above referenced PCTpublications to Ben Haim et al., having International PublicationNumbers WO 97/25098, WO 98/10828, WO 98/10829, WO 98/10830, WO 98/10831,and WO 98/10832. These CCM signal forms (also referred to as ETC signalforms) may be useful for CCM anti-arrhythmia therapy.

In accordance with one preferred embodiment of the present invention,the method for delivering CCM signals to the heart in order to treatarrhythmia includes methods of detection of arrhythmia as is known inthe art. Any of the methods including sensing, event detection andtachy-arrhythmia classification algorithms may be used to detectarrhythmia. For example, PVC detection as achieved by using thesequential activation of ventricles following the atria in every heartbeat, as is well known in the art, may also be used as a method todetect arrhythmia.

The method for delivering CCM signals to the heart in order to treatarrhythmia further includes calculation of the prevalence of arrhythmiaat any given time. In accordance with one preferred embodiment of thepresent invention, calculation of the prevalence of arrhythmia at anygiven time consists of counting the number of detected arrhythmiaepisodes in a given period of time.

Different arrhythmia types may be counted separately when calculatingthe prevalence of arrhythmia. Alternatively or additionally, differentkinds of arrhythmia may be pooled together for calculating theprevalence of arrhythmia. For example, the prevalence of any length ofPVC run (including a single PVC, PVC couplets, PVC triplets and thelike) may be calculated as the sum of all such arrhythmic episodesoccurring in a given period of time.

The calculated prevalence of arrhythmia is compared to a valuerepresenting the level of prevalence of arrhythmia that requires CCMtherapy initiation. The level of prevalence of arrhythmia that requiresCCM therapy initiation is, preferably, set for each patient separatelybased on the arrhythmic history and prognosis of the patient as may beobtained and evaluated by a physician or cardiologist from examinationof the patients ECG trace, other suitable available types of recordedelectrical cardiac activity such as, but not limited to, IEGMrecordings, and recorded medical history.

Once the level of prevalence of arrhythmia required for the initiationof CCM therapy is exceeded by the actual calculated prevalence ofarrhythmia. CCM signal delivery is initiated for a first period of CCMtherapy. The first period of CCM therapy includes a number of heartbeats which may be a preset number of heart beats or may be dependentupon the type or other parameters of the detected arrhythmia, or uponthe calculated prevalence of arrhythmia. Additionally, the parameters ofthe CCM signals delivered to the heart may be preset or may also bedetermined by the type of the detected arrhythmia or by other parametersof the detected arrhythmia, or by the calculated prevalence ofarrhythmia.

During the first period of CCM therapy, arrhythmia detection isperformed in the presence of the delivered CCM signals, as disclosed indetail hereinabove. Upon detection of arrhythmia during the applicationof CCM therapy, CCM signal delivery may be stopped so that another typeof anti-arrhythmic therapy may be employed, depending upon the natureand parameters of the detected arrhythmia. For example, CCM signaldelivery may be stopped if VF is detected during CCM delivery, in orderto deliver a defibrillating shock. Alternatively, parameters relating toCCM delivery, such as, but not limited to, the waveform, duration,amplitude or polarity of the CCM signals, may be modified according toparameters relating to the arrhythmia detected.

Once the first period of CCM therapy ends, detection of arrhythmiacontinues and CCM therapy may be employed again, depending on thearrhythmia detected. For example, a decline in the prevalence ofarrhythmia during or immediately following the application of CCMtherapy, followed by an increase of arrhythmia prevalence once CCMtherapy is stopped, may lead to re-initiation of CCM therapy using thesame CCM signal parameters as in the first period of CCM therapy.However, different parameters such as, but not limited to, duration,waveform, amplitude and polarity of the CCM signals may also be used inthe second period of CCM therapy. For example, a longer duration of CCMtherapy may be used for the second period of CCM delivery.

In accordance with another embodiment of the present invention, themethod for delivering CCM signals to the heart in order to treatarrhythmia includes methods of detecting possible indications ofarrhythmia as are known in the art. For example, T-wave alternans mayserve as an indicator of increased risk of arrhythmia, as disclosed byRichard et al. in an article titled “ELECTROPHYSIOLOGICAL BASIS FOR TWAVE ALTERNANS AS AN INDEX OF VULNERABILITY TO VENTRICULAR FIBRILLATION”published in the Journal of Cardiovascular Electrophysiology, Vol. 5,pp. 445–461 (1994) and incorporated herein by reference.

Once the indications of arrhythmia exceed a certain level, which may bea preset level or may be dependent upon the type or other parameters ofthe indications of arrhythmia detected, CCM therapy may be initiated fora first period of CCM therapy. During the first period of CCM therapy orfollowing the first period of CCM therapy, depending on the type ofarrhythmia indication detected, the CCM signal parameters, such as, butnot limited to, the duration, waveform, amplitude and polarity of theCCM signal, may be altered. Additionally or alternatively, anotherperiod of CCM therapy may be employed based on the arrhythmiaindications detected following a period of CCM therapy.

Preferably, the detection of arrhythmia and of indications of arrhythmiais performed simultaneously, and the delivery of CCM therapy isinitiated either if an arrhythmia is detected, as disclosed hereinabove,or if arrhythmia indications are detected, as disclosed hereinabove.

Reference is now made to FIGS. 5–8 which are schematic diagramsillustrating different preferred embodiments of the anti-arrhythmicdevice of the present invention which are adapted for delivering CCMsignals having anti arrhythmic effects to the heart.

FIG. 5 illustrates an external anti-arrhythmic device 150. The device150 includes a controller unit 152. The controller unit 152 may be anytype of controller unit such as a micro-controller, a microprocessor, orthe like. The controller unit 152 is operatively connected to a pacingunit 154, a CCM unit 156 and a cardioversion/defibrillation unit 158 forcontrolling the operation thereof. The controller 152 is also connectedto a user interface 160 for providing output to a user and for receivingcommands from the user. The user interface may be any type of userinterface, such as but not limited to, a keyboard, a light pen, atouch-pad a pointing device, a touch sensitive display screen or anycombination thereof. The controller 152 is also connected to a displayunit 162 for providing visual output to the user of the device 150, suchas but not limited to graphic output, alphanumeric output, graphic signsand icons, and any combination thereof. The display unit may be any typeof display unit known in the art, such as a cathode ray tube display, aliquid crystal display, a plasma display, a photoluminescent display,and the like.

The controller 152 is also connected to a data storage unit 164 forstoring and retrieving data and information by the user of the device151 and by the controller unit 152, such as but not limited to, amagnetic disc storage device, a removable magnetic media storage device,a solid state memory storage device, an opto-magnetic storage device, anoptical storage device, or any other type of device for storing digitalinformation, or other data types, known in the art.

The controller 152 is also suitably connected to a memory unit 166 forstoring and retrieving data and information by the controller unit 152.The memory unit 166 may include one or more memory devices (not shown)for storing and retrieving data. The memory unit 166 may include anyread-only memory devices and/or read-write memory devices for storageand retrieval of data, as is known in the art.

The device 150 is connectable to one or more leads 170 as is known inthe art, the leads may be any type of suitable leads which are known inthe art and which include one or more electrodes for pacing, sensing,delivering cardioversion/defibrillation therapy and delivering CCMsignals to the heart. The leads 170 may be implantable or temporaryleads. The device 150 further includes one or more sensing units 168.The sensing units 168 are connectable to one or more electrodes (notshown) included in the leads 170. The sensing units are adapted forsensing electrical depolarization events of the heart as is well knownin the art. The sensing units may also includes amplification circuitry(not shown) for amplifying the sensed signals as is known in the art.The sensing electrodes (not shown) may be disposed at or about aplurality of cardiac sites. For example, in accordance with onenon-limiting example, the sensing units 168 are connected to sensingelectrodes (not shown) disposed at or about the left atrium, the rightventricle and the left ventricle of the heart.

The device 150 further includes a detection and classification unit 172which is operatively connected to the sensing units 162 and to thecontroller unit 152, and is operative to detect depolarization events inthe electrical signals sensed by the sensing units 168. The detectionand classification unit 172 is also operative to classify the heart ratebased on the detected events in order to detect various types ofarrhythmias as is known in the art. The detection and classificationunit 172 may be any detection and classification unit known in the artand suitable for classifying arrhythmias.

The pacing unit 154 may be operatively connected to one or moreelectrodes (not shown) of the leads 170. The electrodes may be dedicatedpacing electrodes or any other type of electrode which may also be usedfor sensing, delivering CCM therapy, or deliveringcardioversion/defibrillation therapy. The pacing unit 154 may be adaptedto deliver anti-bradycardia pacing therapy as is well known in the art.In accordance with one non-limiting example, the pacing unit isoperatively connected to pacing electrodes disposed at or about theright atrium (RA) and the right ventricle (RV) and may be used foruni-ventricular or biventricular pacing as is known in the art. Otherpacing forms or electrodes configurations may also be used, and areincluded within the scope of the present invention.

It is noted that the device 150 may also include one or more timingunits (not shown) connected to the controller unit 152 or to the pacingunit 154 for providing timing signals (clocking signals) to thecontroller unit 152 or to the pacing unit 154.

The device 150 also includes a power source 165 for providing power tothe various components of the device 150. The power source 165 issuitably operatively connected (connections not shown for the sake ofclarity of illustration) to provide electrical energy the components ofthe device 150 as is known in the art. The power source 165 may be anelectrochemical cell or a battery (primary or rechargeable), or the likebut may be any other suitable power source for providing electricalpower which is known in the art. It is noted that while the power source165 is shown as included within the device 150, the power source 165 maybe also disposed externally to the device 150. For example, the powersource 165 may be a power source such as, but not limited to, aconditioned or regulated DC or AC power supply, operatively connected tothe mains power supply (not shown) as is known in the art.

The CCM unit 156 may be used for applying CCM signals to the heart as isknown in the art and disclosed in detail hereinabove. The application ofthe CCM signals is performed through one or more electrodes or electrodepairs which are within the leads 170. The electrodes may be disposed ator about one or more sites in the heart, such as but not limited to, oneor more parts of the left ventricle.

The controller 152 controls the delivery of CCM signals to the heart asdisclosed hereinabove, using timing methods as disclosed in the abovereferenced co-pending US patent applications to Mika et al., and in thecorresponding PCT applications. The CCM signals may be used formodifying the cardiac contractility and the cardiac output as isdisclosed hereinabove and known in the art. Additionally, the controller152 may also control the CCM unit to deliver CCM signals as therapy fora detected tachy-arrhythmia which is detected by the detection andclassification unit 172 using any suitable detection and classificationmethods known in the art or disclosed hereinabove. To initiate a CCMtherapy period as disclosed hereinabove, the controller 152 may initiateCCM therapy by controlling the CCM unit 156 to deliver CCM signals tothe heart through the appropriate electrodes (not shown) of the leads170. The method of delivery of the CCM signals as anti-arrhythmiatherapy is disclosed in detail hereinabove.

The cardioversion/defibrillation unit 158 of the device 150 may be anycardioversion/defibrillation unit known in the art and disclosedhereinabove. The cardioversion/defibrillation unit 158 may operate todeliver cardioversion therapy and or defibrillation shock therapy to theheart through suitable cardioversion and/or defibrillation electrodesdisposed in or about the heart, as is known in the art. The electrodes(not shown) used for delivering cardioversion and/or defibrillationtherapy may be epicardial electrodes, transvenous electrodes,intracardiac electrodes, or any other type of suitable electrodes knownin the art.

If the tachy-arrhythmia does not respond well to the anti-arrhythmic CCMtherapy, the controller 152 may control the cardioversion/defibrillationunit 158 to deliver other suitable types of anti-tachycardia therapysuch as for example, cardioversion therapy or defibrillation shocktherapy as disclosed hereinabove.

Typically, the device 150 is an external non-implanted device which maybe used for patient supporting and therapy in cardiac patients such ascardiac patients in intensive care unit after cardiac surgery, or aheart condition. In operation, the device 150 is suitably connected tothe appropriate leads 170 which are inserted into the patient and may beused to apply different forms of cardiac therapy as disclosedhereinabove as well as td record and/or monitor the patient's cardiacconditions and the effects of different therapy types on the heart. Thedevice may also be used in data recording sessions in the patient whichmay be used for recording data and for processing, analyzing anddisplaying data. The data may be used by a physician or cardiologist fordetermining various thresholds and parameter values of the pacingsensing, CCM delivery (including CCM alert window parameters), andcardioversion or defibrillation parameters.

It is noted that the external device 150 may also be implemented withouta pacing unit FIG. 6 illustrates such an external anti-arrhythmic device180 which does not include a pacing unit. The device 180 is similar tothe device 150, except that the pacing unit 154 is absent in the device180. Thus, the device 180 does not provide pacing capabilities andtherefore cannot be used for providing anti-bradycardia pacing therapyto the patient. The operation and use of the device 180 for detectingtachy-arrhythmia and for providing various types of anti-arrhythmictherapy types including, inter alia, CCM signal anti-arrhythmic therapyis similar to the operation and use of the device 150 as disclosed indetail hereinabove. The device 180 may be useful for treating patientswho are not in need of pacing therapy. The device 160 is connectable toleads 170A which may be identical to the leads 170 of the device 150,but may also be different from leads 170 of the device 150. Since thedevice 160 does not include a pacing unit, there is no need for pacingelectrodes therefore at least some of the leads 170A may be leadsincluding a smaller number of electrodes. However, frequently, thepacing unit and the sensing units may use the same electrodes forsensing and pacing, therefore, the leads 170A may be similar to theleads 170, except that no pacing is performed through the sensingelectrodes.

It is further noted that, implantable devices with anti-arrhythmic CCMtherapy capabilities may also be constructed. FIG. 7 illustrates animplantable anti-arrhythmic device 190 having anti-arrhythmic CCMtherapy capabilities. The device 190 is similar in operation to thedevice 150 of FIG. 5 except that the device 190 does not include theuser interface 160, the display unit 162 and the data storage unit 164which are included in the external device 150. The implantable device190 is adapted for being chronically implanted in a cardiac patient.Therefore, the device 190 includes a pacing unit 154A, sensing units168A, a CCM unit 156A, a cardiovertion/defibrillation unit 158A, acontroller unit 152A, a memory unit 166A, and a detection andclassification unit 172A which are functionally and operatively similarto the pacing unit 154, the sensing units 168, the CCM unit 156, thecardiovertion/defibrillation unit 158, the controller unit 152, thememory unit 166, and the detection and classification unit 172,respectively, of the device 150 of FIG. 5. However, the pacing unit154A, the sensing units 168A, the CCM unit 156A, thecardiovertion/defibrillation unit 158A, the controller unit 152A, thememory unit 166A, and the detection and classification unit 172A may beminiaturized to adapt them for operating in an implanted device as isknown in the art. The device 190 is operatively connectable to leads170B. The leads 1.708 may be similar to the leads 170 of FIG. 5, exceptthat the leads 170B must be implantable leads while the leads 170 may beimplantable leads or temporary insertable leads.

It is noted that the implantable device 190 may also include a telemetryunit (not shown) operatively connected to the controller 152A fortelemetrically communicating with a telemetry transceiver (not shown)disposed outside the patient as is known in the art. The telemetry unit(if included in the device) may be used to program data and instructionsor commands into the memory unit 166A for wirelessly changing theoperating programs of the device 190 and for telemetrically transmittingdata related to the patient's cardiac condition to the externaltelemetry transceiver for patient monitoring and for data analysis.

It is further noted that the implantable device 190 may also include oneor more timer units (not shown) operatively connected to the controllerunit 152A for providing timing or clock signals thereto.

FIG. 8 illustrates an implantable anti-arrhythmic device 200 which doesnot include a pacing unit. The device 200 is similar to the device 190of FIG. 7, except that the pacing unit 154A is not included in thedevice 200. Thus, the device 200 does not provide pacing capabilitiesand therefore cannot be used for providing anti-bradycardia pacingtherapy to the patient. The operation and use of the device 200 fordetecting tachy-arrhythmia and for providing various types ofanti-arrhythmic therapy types including, inter alia, CCM signalanti-arrhythmic therapy is as disclosed in detail hereinabove. Thedevice 200 may be useful for treating patients who are not in need ofpacing therapy. The device 200 is connectable to leads 170C which may beimplantable leads similar, with respect to electrode number andconfiguration, to the leads 170A or 170B of the devices 180 and 190,respectively, but may also be different from leads 170A and 170B. Sincethe device 200 does not include a pacing unit, there is no need forpacing electrodes, therefore at least some of the leads 170C may beleads including a smaller number of electrodes than the number ofelectrodes included in the leads 170B of the implantable device 190.However, frequently, the pacing unit and the sensing units may use thesame electrodes for sensing and pacing. Thus, the leads 170C may besimilar, with respect to electrode number and configuration, to theleads 170B, except that no pacing is performed through the sensingelectrodes of the leads when they are connected to the device 200. Theleads 170C may be implantable leads adapted to being chronicallyimplanted.

Each of the implantable devices 100, 190 and 200 also includes a powersource 165 for providing power to the various components of the devices100, 190 and 200, respectively. The power source 165 is suitablyoperatively connected (connections not shown for the sake of clarity ofillustration) to provide electrical energy the components of each of thedevices 100, 190 and 200, as is known in the art. The power source 165may be an electrochemical cell or a battery (primary or rechargeable),or the like, but may be any other suitable power source for providingelectrical power to an implantable device which is known in the art.

In accordance with another preferred embodiment of the present inventiona combined multi-modal cardio-therapeutic device may be constructedwhich will controllably use a combination of all the above disclosedtherapeutic modalities and methods.

The general cardio-therapeutic device may be similar in construction toany of the devices 100, 150 and 190 of the present invention. However,the multi-modal cardio-therapy device may include software or suitableembedded program or programs which enable it to controllably andselectively apply any of the therapeutic modalities disclosedhereinabove based on the cardiac condition of the patient, but may alsobe programmed or controlled by a user such as a physician orcardiophysiologist to selectably disable or enable any of thecardiotherapy modalities available on the device.

For example, the implantable device 100 of FIG. 4 is capable of applyingto the heart an anti-bradycardia pacing therapy mode, a plurality ofanti-tachycardia therapy modes, including but not limited tocardioversion therapy modes, ATP modes, defibrillating shock therapy,and CCM signal anti-arrhythmic therapy mode. In addition to theseanti-arrhythmic therapy modalities, the device 100 may also apply to theheart a cardiac contractility modulating therapy which is non-related torhythm disturbances but is directed to modulate the contractility of themyocardium to achieve modulation of the cardiac output withoutmodulating the heart rate. In a non-limiting example, the last modalitymay be used to increase the cardiac output of CHF patients by increasingthe contractility of the left ventricle without substantially increasingthe heart rate.

When the device 100 is operated in the full multi-modal capacity, themicroprocessor unit 106 is operative to control and coordinate theoperation and timing of the pacing unit 102, the anti-tachyarrhythmicunit 118, and the CCM unit 108, in accordance with the data received andprocessed by the microprocessor 106. Thus, the device 100 may providecoordinated multi modal therapies to the heart. The device 100 may applyCCM therapy to modulate the cardiac output when CCM therapy isindicated. The device 100 may also apply, simultaneously or separately,pacing therapy as is known in the art by controlling the pacing unit102. The device 100 may apply anti-arrhythmic therapy to the heart basedon the detection and classification methods disclosed hereinabove andknown in the art implemented by using the output of the detecting unit116.

The device 100 coordinates the application of the different therapymodalities such that, on one hand, the CCM signal induced artifacts donot interfere with the operation of arrhythmia detection andclassification algorithms, as disclosed in detail hereinabove, and onthe other hand, the CCM unit 108 may be utilized to deliver controlledanti-arrhythmic CCM therapy when an arrhythmia is detected as disclosedhereinabove. The device 100 also controls the anti-tachy-arrhythmic unit118 to controllably and selectively apply tiered multi-modal therapy tothe heart, including but not limited to, an ATP therapy mode, acardioversion therapy mode and a defibrillation shock therapy mode,depending on the arrhythmia type detected by the classificationalgorithm operative on the microprocessor 106.

An aspect of the multi modal cardiotherapy devices of the presentinvention such as the exemplary device 100 is that while the device iscapable of applying all the therapy modes available in a coordinatedfashion based on the methods disclosed hereinabove, one or more of thetherapy modes may be selectively disabled or switched off by suitableprogramming of the device 100. For example, the device 100 may beprogrammed to stop the delivery of cardiac output modulating therapy forthe purpose of modulating the cardiac output, while still enabling theapplication of CCM signal delivery initiated as antiarrhythmic therapyfollowing the detection of an arrhythmia. Similarly, the pacing therapymay be disabled while all the other therapy modalities are leftoperative. Other combinations of selective disabling of specific therapymodalities may also be possible. Such selective modality control may beadvantageous since they may help in conserving battery power when one ormore of the therapy modalities is not requested due to a change in thepatient's cardiac conditions or to any other reason, while being fullyreversible if the cardiac situation changes again.

The advantage of such a multi modal device, whether it is an externaldevice or an implantable internal device, is that it provides the widevariety of possible cardiac modalities as disclosed hereinabove in onedevice, enables their use in the patient in a coordinated and controlledmanner, and particularly in implantable versions of the device, obviatesthe need to implant multiple implantable cardiotherapy devices in thepatient, such as for example, the implantation of a separate implantablecardiovertion/defibrillation device and a separate CCM device within thesame patient which anyhow may be very difficult or even impossible tooperate simultaneously in one patient due to the CCM induced artifactproblem disclosed hereinabove.

It will be appreciated that the preferred embodiments disclosedhereinabove and illustrated in the drawings are given by way of exampleonly and that many variations and modifications of the present inventionmay be made which are within the scope and spirit of the presentinvention.

1. A method for operating a multi-modal cardiotherapy device to delivermulti-modal cardiotherapy to a heart, the method comprising the stepsof: providing a device configured for delivering cardiac contractilitymodulating signals and a plurality of anti-arrhythmic therapy modalitiesto said heart; applying cardiac contractility modulating signals to saidheart to modulate the contractility of at least a portion of said heart;detecting an arrhythmia or indications of possible arrhythmia in saidheart; delivering to said heart an anti-arrhythmic therapy selected fromsaid plurality of anti-arrhythmic therapy modalities based on the typeof said arrhythmia or said indications detected in said step ofdetecting; and coordinating the application of cardiac contractilitymodulating signals of said step of applying with the delivering of saidanti-arrhythmic therapy of said step of delivering.
 2. The methodaccording to claim 1 wherein said plurality of anti-arrhythmic therapymodalities comprises cardiac contractility modulating signalanti-arrhythmic therapy and one or more anti-arrhythmic therapymodalities selected from defibrillating shock therapy, cardiovertingshock therapy, anti-tachycardia pacing therapy, variable energy shocktherapy, anti-bradycardia pacing therapy and any combination thereof. 3.The method according to claim 2 wherein said cardiac contractilitymodulating signal anti-arrhythmic therapy comprises delivering one ormore of said cardiac contractility modulating signals to said heart forreducing the prevalence of arrhythmic episodes detected in said heart.4. The method according to claim 1 wherein said step of applying cardiaccontractility modulating signals to said heart is performed formodulating the cardiac output of said heart.
 5. The method according toclaim 1 wherein said step of coordinating comprises the step ofterminating the applying of cardiac contractility modulating signals tosaid heart of said step of applying, prior to or upon said delivering tosaid heart of said anti-arrhythmic therapy.
 6. The method according toclaim 5 wherein said step of coordinating comprises the step of renewingthe applying of cardiac contractility modulating signals to said heartafter said delivering to said heart of said anti-arrhythmic therapy isterminated.
 7. The method according to claim 1 wherein said indicationsof possible arrhythmia include the detection of T-wave alternans in saidheart.
 8. The method according to claim 1 wherein said step of detectingfurther includes the step of determining the heart rate of said heartand disabling the applying of said cardiac contractility modulatingsignals to said heart within the duration of a cardiac contractilitymodulating signal free time period if said heart rate is larger than afirst threshold value.
 9. The method according to claim 1 wherein saidstep of detecting further includes the step of enabling the applying ofsaid cardiac contractility modulating signals to said heart if noarrhythmia or indications of possible arrhythmia are detected within theduration of said cardiac contractility modulating signal free timeperiod.
 10. A method for operating a multi-modal cardiotherapy device todeliver multi-modal cardiotherapy to a heart, the device is configuredfor delivering cardiac contractility modulating signals and a pluralityof anti-arrhythmic therapy modalities to said heart, the methodcomprising the steps of: applying cardiac contractility modulatingsignals to said heart to modulate the cardiac output of said heart;detecting an arrhythmia or indications of possible arrhythmia in saidheart; delivering to said heart an anti-arrhythmic therapy selected fromsaid plurality of anti-arrhythmic therapy modalities based on the typeof said arrhythmia or said indications detected in said step ofdetecting; and coordinating the application of cardiac contractilitymodulating signals of said step of applying with the delivering of saidanti-arrhythmic therapy of said step of delivering.
 11. The methodaccording to claim 10 wherein said plurality of anti-arrhythmic therapymodalities comprises cardiac contractility modulating signalanti-arrhythmic therapy and one or more anti-arrhythmic therapymodalities selected from defibrillating shock therapy, cardiovertingshock therapy, anti-tachycardia pacing therapy, variable energy shocktherapy, anti-bradycardia pacing therapy and any combination thereof.12. The method according to claim 11 wherein said cardiac contractilitymodulating signal antiarrhythmic therapy comprises delivering one ormore of said cardiac contractility modulating signals to said heart forreducing the prevalence of arrhythmic episodes detected in said heart.13. The method according to claim 10 wherein said step of applyingcardiac contractility modulating signals to said heart is performed formodulating the cardiac output of said heart.
 14. The method according toclaim 10 wherein said step of coordinating comprises the step ofterminating the applying of cardiac contractility modulating signals tosaid heart of said step of applying, prior to or upon said delivering tosaid heart of said anti-arrhythmic therapy.
 15. The method according toclaim 14 wherein said step of coordinating comprises the step ofrenewing the applying of cardiac contractility modulating signals tosaid heart after said delivering to said heart of said anti-arrhythmictherapy is terminated.
 16. The method according to claim 10 wherein saidindications of possible arrhythmia include the detection of T-wavealternans in said heart, as an indication of a possible cardiacarrhythmia.
 17. The method according to claim 10 wherein said step ofdetecting further includes the step of determining the heart rate ofsaid heart and disabling the applying of said cardiac contractilitymodulating signals to said heart within the duration of a cardiaccontractility modulating signal free time period if said heart rate islarger than a first threshold value.
 18. The method according to claim10 wherein said step of detecting further includes the step of enablingthe applying of said cardiac contractility modulating signals to saidheart if no arrhythmia or indications of possible arrhythmia aredetected within the duration of said cardiac contractility modulatingsignal free time period.
 19. A multi-modal cardiotherapy devicecomprising: an anti-arrhythmic unit for delivering anti-arrhythmictherapy to said heart; a cardiac contractility modulating unitconfigured for delivering cardiac contractility modulating signals tosaid heart for modulating the cardiac contractility of at least aportion of said heart, and for applying anti-arrhythmic cardiaccontractility modulating signal therapy to said heart; a sensing unitfor sensing electrical signals related to electrical activity of saidheart to provide an output signal; a detecting unit operativelyconnected to said sensing unit for receiving said output signal of saidsensing unit and for detecting in said output signal cardiac events ofsaid heart; a controller unit operatively connected to saidanti-arrhythmic unit, said cardiac contractility modulating unit andsaid detecting unit; for processing the output of said detecting unit todetect a cardiac arrhythmia or indications of possible arrhythmia,controlling the application of said anti-arrhythmic therapy by saidanti-arrhythmic unit, and for controlling the application of saidanti-arrhythmic cardiac contractility modulating signal therapy, and themodulating of said cardiac contractility of said portion of said heartby said cardiac contractility modulating unit; and at least one powersource for providing power to said anti-arrhythmic therapy unit, saidcardiac contractility modulating unit, said sensing unit, said detectingunit, and said controller unit.
 20. The multi-modal cardiotherapy deviceaccording to claim 19, wherein said anti-arrhythmic unit is configuredfor delivering to said heart multiple modes of ant-arrhythmic therapyselected from anti-bradycardia pacing therapy, defibrillating shocktherapy, cardioverting shock therapy, anti-tachycardia pacing therapy,variable energy shock therapy, and any combination thereof.
 21. Themulti-modal cardiotherapy device according to claim 19, wherein saidcontroller unit is configured for coordinating the application to saidheart of anti-arrhythmic therapy by said anti-arrhythmic unit with theapplication to said heart of said anti-arrhythmic cardiac contractilitymodulating signal therapy by said cardiac contractility modulating unit.22. The multi-modal cardiotherapy device according to claim 19, whereinsaid controller unit is configured for coordinating the application tosaid heart of anti-arrhythmic therapy by said anti-arrhythmic unit withsaid modulating of said cardiac contractility by said cardiaccontractility modulating unit.
 23. The multi-modal cardiotherapy deviceaccording to claim 19, wherein said anti-arrhythmic unit comprises apacing unit configured for pacing at least one chamber of said heart.24. The multi-modal cardiotherapy device according to claim 19 whereinsaid cardiac contractility modulating unit is configured forcontrollably delivering cardiac contractility modulating signalanti-arrhythmic therapy to said heart by controllably delivering one ormore of said cardiac contractility modulating signals to said heart forreducing the prevalence of arrhythmic episodes detected in said heart.25. The multi-modal cardiotherapy device according to claim 19 whereinsaid cardiac contractility modulating unit is configured for modulatingthe cardiac output of said heart by delivering said cardiaccontractility modulating signals to said heart.
 26. The multi-modalcardiotherapy device according to claim 19 wherein said controller unitis configured for terminating the applying of cardiac contractilitymodulating signals to said heart prior to or upon said delivering tosaid heart of said anti-arrhythmic therapy.
 27. The multi-modalcardiotherapy device according to claim 19 wherein said controller unitis configured for renewing the applying of cardiac contractilitymodulating signals to said heart after said delivering to said heart ofsaid anti-arrhythmic therapy is terminated.
 28. The multi-modalcardiotherapy device according to claim 19 wherein said detecting unitis configured for detecting T-wave alternans in said heart, as anindication of a possible cardiac arrhythmia.
 29. The multi-modalcardiotherapy device according to claim 19 further including electrodesoperatively connected to said anti-arrhythmic unit, said cardiaccontractility modulating unit, and said sensing unit, for deliveringsaid anti-arrhythmic therapy to said heart, for applying said cardiaccontractility modulating signals to said heart, and for sensing saidelectrical signals, respectively.
 30. The multi-modal cardiotherapydevice according to claim 19 wherein said controller unit is configuredfor determining the heart rate of said heart and for disabling saidmodulating of said cardiac contractility of said portion of said heartby said cardiac contractility modulating unit within the duration of acardiac contractility modulating signal free time period if said heartrate is larger than a first threshold value.
 31. The multi-modalcardiotherapy device according to claim 19 wherein said controller unitis configured for enabling said modulating of said cardiac contractilityof said portion of said heart by said cardiac contractility modulatingunit if no arrhythmia or indications of possible arrhythmia are detectedwithin the duration of said cardiac contractility modulating signal freetime period.
 32. A multi-modal cardiotherapy device comprising:anti-arrhythmic means for delivering multiple modes of anti-arrhythmictherapy to said heart; cardiac contractility modulating means configuredfor delivering cardiac contractility modulating signals to said heart,for modulating the cardiac contractility of at least a portion of saidheart, and for applying anti-arrhythmic cardiac contractility modulatingsignal therapy to said heart; sensing means for sensing electricalsignals related to cardiac activity sensed at said heart; detectingmeans operatively connected to said sensing means for receiving theoutput signal of said sensing means and for detecting cardiacdepolarization events of said heart; controller means operativelyconnected to said anti-arrhythmic means, said cardiac contractilitymodulating means and said detecting means, for processing the output ofsaid detecting means to detect a cardiac arrhythmia or indications ofpossible arrhythmia, controlling the application of said anti-arrhythmictherapy modes by said anti-arrhythmic means, and for controlling theapplication of said anti-arrhythmic cardiac contractility modulatingsignal therapy, and the modulating of said cardiac contractility by saidcardiac contractility modulating means; and means for providing power tosaid anti-arrhythmic means, said cardiac contractility modulating means,said sensing means, said detecting means and said controller means. 33.The multi-modal cardiotherapy device according to claim 32, wherein saidanti-arrhythmic means is configured for delivering to said heartmultiple modes of anti-arrhythmic therapy selected from anti-bradycardiapacing therapy, defibrillating shock therapy, cardioverting shocktherapy, anti-tachycardia pacing therapy, variable energy shock therapy,and any combination thereof.
 34. The multi-modal cardiotherapy deviceaccording to claim 32, wherein said controller means is configured forcoordinating the application to said heart of anti-arrhythmic therapy bysaid anti-arrhythmic means with the application to said heart of saidanti-arrhythmic cardiac contractility modulating signal therapy by saidcardiac contractility modulating means.
 35. The multi-modalcardiotherapy device according to claim 32, wherein said controllermeans is configured for coordinating the application to said heart ofanti-arrhythmic therapy by said anti-arrhythmic means with saidmodulating of said cardiac contractility by said cardiac contractilitymodulating means.
 36. The multi-modal cardiotherapy device according toclaim 32, wherein said anti-arrhythmic means comprises pacing meansconfigured for pacing at least one chamber of said heart.
 37. Themulti-modal cardiotherapy device according to claim 32 wherein saidcardiac contractility modulating means is configured for controllablydelivering cardiac contractility modulating signal anti-arrhythmictherapy to said heart by controllably delivering one or more of saidcardiac contractility modulating signals to said heart for reducing theprevalence of arrhythmic episodes detected in said heart.
 38. Themulti-modal cardiotherapy device according to claim 32 wherein saidcardiac contractility modulating means is configured for modulating thecardiac output of said heart by delivering said cardiac contractilitymodulating signals to said heart.
 39. The multi-modal cardiotherapydevice according to claim 32 wherein said controller means is configuredfor terminating the applying of cardiac contractility modulating signalsto said heart prior to or upon said delivering to said heart of saidanti-arrhythmic therapy.
 40. The multi-modal cardiotherapy deviceaccording to claim 32 wherein said controller means is configured forrenewing the applying of cardiac contractility modulating signals tosaid heart after said delivering to said heart of said anti-arrhythmictherapy is terminated.
 41. The multi-modal cardiotherapy deviceaccording to claim 32 wherein said detecting means is configured fordetecting T-wave alternans in said heart, as an indication of a possiblecardiac arrhythmia.
 42. The multi-modal cardiotherapy device accordingto claim 32 further including electrode means operatively connected tosaid anti-arrhythmic means, said cardiac contractility modulating meansand said sensing means, for delivering said anti-arrhythmic therapy tosaid heart, for applying said cardiac contractility modulating signalsto said heart, and for sensing said electrical signals, respectively.43. The multi-modal cardiotherapy device according to claim 32 whereinsaid controller means is configured for determining the heart rate ofsaid heart and for disabling said modulating of said cardiaccontractility of said portion of said heart by said cardiaccontractility modulating means within the duration of a cardiaccontractility modulating signal free time period if said heart rate islarger than a first threshold value.
 44. The multi-modal cardiotherapydevice according to claim 32 wherein said controller means is configuredfor enabling said modulating of said cardiac contractility of saidportion of said heart by said cardiac contractility modulating means ifno arrhythmia or indications of possible arrhythmia are detected withinthe duration of said cardiac contractility modulating signal free timeperiod.